Troponins, intrinsic disorder, and cardiomyopathy

References

Alfares, A.A., Kelly, M.A., McDermott, G., Funke, B.H., Lebo, M.S., Baxter, S.B., Shen, J., McLaughlin, H.M., Clark, E.H., Babb, L.J., et al. (2015). Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 17, 880–8.10.1038/gim.2014.205Suche in Google Scholar PubMed

Apweiler, R., Bairoch, A., Wu, C.H., Barker, W.C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M., et al. (2004). UniProt: the universal protein knowledgebase. Nucleic Acids Res. 32, D115–D119.10.1093/nar/gkh131Suche in Google Scholar PubMed PubMed Central

Bunk, D.M., Dalluge, J.J., and Welch, M.J. (2000). Heterogeneity in human cardiac troponin I standards. Anal. Biochem. 284, 191–200.10.1006/abio.2000.4710Suche in Google Scholar PubMed

Cheng, Y., LeGall, T., Oldfield, C.J., Mueller, J.P., Van, Y.Y., Romero, P., Cortese, M.S., Uversky, V.N., and Dunker, A.K. (2006). Rational drug design via intrinsically disordered protein. Trends Biotechnol. 24, 435–442.10.1016/j.tibtech.2006.07.005Suche in Google Scholar PubMed

Cheng, Y., Rao, V., Tu, A.Y., Lindert, S., Wang, D., Oxenford, L., McCulloch, A.D., McCammon, J.A., and Regnier, M. (2015). Troponin I mutations R146G and R21C alter cardiac troponin function, contractile properties, and modulation by protein kinase A (pKA)-mediated phosphorylation. J. Biol. Chem. 290, 27749–27766.10.1074/jbc.M115.683045Suche in Google Scholar PubMed PubMed Central

Cortese, M.S., Uversky, V.N., and Dunker, A.K. (2008). Intrinsic disorder in scaffold proteins: getting more from less. Prog. Biophys. Mol. Biol. 98, 85–106.10.1016/j.pbiomolbio.2008.05.007Suche in Google Scholar PubMed PubMed Central

Daughdrill, G.W., Pielak, G.J., Uversky, V.N., Cortese, M.S., and Dunker, A.K. (2005). Natively disordered proteins. In Handbook of Protein Folding, J. Buchner and T. Kiefhaber, eds. (Weinheim, Germany: Wiley-VCH, Verlag GmbH & Co. KGaA), pp. 271–353.10.1002/9783527619498.ch41Suche in Google Scholar

Disfani, F.M., Hsu, W.L., Mizianty, M.J., Oldfield, C.J., Xue, B., Dunker, A.K., Uversky, V.N., and Kurgan, L. (2012). MoRFpred, a computational tool for sequence-based prediction and characterization of short disorder-to-order transitioning binding regions in proteins. Bioinformatics 28, i75–i83.10.1093/bioinformatics/bts209Suche in Google Scholar PubMed PubMed Central

Dong, X.T., Sumandea, C.A., Chen, Y.C., Garcia-Cazarin, M.L., Zhang, J., Balke, C.W., Sumandea, M.P., and Ge, Y. (2012). Augmented phosphorylation of cardiac troponin I in hypertensive heart failure. J. Biol. Chem. 287, 848–857.10.1074/jbc.M111.293258Suche in Google Scholar PubMed PubMed Central

Dosztanyi, Z., Csizmok, V., Tompa, P., and Simon, I. (2005). IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics 21, 3433–3434.10.1093/bioinformatics/bti541Suche in Google Scholar PubMed

Dosztanyi, Z., Chen, J., Dunker, A.K., Simon, I., and Tompa, P. (2006). Disorder and sequence repeats in hub proteins and their implications for network evolution. J. Proteome Res. 5, 2985–2995.10.1021/pr060171oSuche in Google Scholar

Dosztanyi, Z., Meszaros, B., and Simon, I. (2009). ANCHOR: web server for predicting protein binding regions in disordered proteins. Bioinformatics 25, 2745–2746.10.1093/bioinformatics/btp518Suche in Google Scholar

Dunker, A.K. and Obradovic, Z. (2001). The protein trinity–linking function and disorder. Nat. Biotechnol. 19, 805–806.10.1038/nbt0901-805Suche in Google Scholar

Dunker, A.K. and Uversky, V.N. (2008). Signal transduction via unstructured protein conduits. Nat. Chem. Biol. 4, 229–230.10.1038/nchembio0408-229Suche in Google Scholar

Dunker, A.K. and Uversky, V.N. (2010). Drugs for ‘protein clouds’: targeting intrinsically disordered transcription factors. Curr. Opin. Pharmacol. 10, 782–788.10.1016/j.coph.2010.09.005Suche in Google Scholar

Dunker, A.K., Garner, E., Guilliot, S., Romero, P., Albrecht, K., Hart, J., Obradovic, Z., Kissinger, C., and Villafranca, J.E. (1998). Protein disorder and the evolution of molecular recognition: theory, predictions and observations. Pac. Symp. Biocomput. 473–484.Suche in Google Scholar

Dunker, A.K., Obradovic, Z., Romero, P., Garner, E.C., and Brown, C.J. (2000). Intrinsic protein disorder in complete genomes. Genome Inform Ser Workshop Genome Inform. 11, 161–171.Suche in Google Scholar

Dunker, A.K., Lawson, J.D., Brown, C.J., Williams, R.M., Romero, P., Oh, J.S., Oldfield, C.J., Campen, A.M., Ratliff, C.M., Hipps, K.W., et al. (2001). Intrinsically disordered protein. J. Mol. Graph. Model. 19, 26–59.10.1016/S1093-3263(00)00138-8Suche in Google Scholar

Dunker, A.K., Brown, C.J., Lawson, J.D., Iakoucheva, L.M., and Obradovic, Z. (2002a). Intrinsic disorder and protein function. Biochemistry 41, 6573–6582.10.1021/bi012159+Suche in Google Scholar

Dunker, A.K., Brown, C.J., and Obradovic, Z. (2002b). Identification and functions of usefully disordered proteins. Adv. Protein Chem. 62, 25–49.10.1016/S0065-3233(02)62004-2Suche in Google Scholar

Dunker, A.K., Cortese, M.S., Romero, P., Iakoucheva, L.M., and Uversky, V.N. (2005). Flexible nets: The roles of intrinsic disorder in protein interaction networks. FEBS J. 272, 5129–5148.10.1111/j.1742-4658.2005.04948.xSuche in Google Scholar PubMed

Dunker, A.K., Oldfield, C.J., Meng, J., Romero, P., Yang, J.Y., Chen, J.W., Vacic, V., Obradovic, Z., and Uversky, V.N. (2008a). The unfoldomics decade: an update on intrinsically disordered proteins. BMC Genomics 9(Suppl. 2), S1.10.1186/1471-2164-9-S2-S1Suche in Google Scholar PubMed PubMed Central

Dunker, A.K., Silman, I., Uversky, V.N., and Sussman, J.L. (2008b). Function and structure of inherently disordered proteins. Curr. Opin. Struct. Biol. 18, 756–764.10.1016/j.sbi.2008.10.002Suche in Google Scholar

Dyson, H.J. and Wright, P.E. (2002). Coupling of folding and binding for unstructured proteins. Curr. Opin. Struct. Biol. 12, 54–60.10.1016/S0959-440X(02)00289-0Suche in Google Scholar

Dyson, H.J. and Wright, P.E. (2005). Intrinsically unstructured proteins and their functions. Nat. Rev. Mol. Cell Biol. 6, 197–208.10.1038/nrm1589Suche in Google Scholar PubMed

Ekman, D., Light, S., Bjorklund, A.K., and Elofsson, A. (2006). What properties characterize the hub proteins of the protein-protein interaction network of Saccharomyces cerevisiae? Genome Biol. 7, R45.10.1186/gb-2006-7-6-r45Suche in Google Scholar PubMed PubMed Central

Fuxreiter, M., Toth-Petroczy, A., Kraut, D.A., Matouschek, A., Lim, R.Y., Xue, B., Kurgan, L., and Uversky, V.N. (2014). Disordered proteinaceous machines. Chem. Rev. 114, 6806–6843.10.1021/cr4007329Suche in Google Scholar PubMed PubMed Central

Gilda, J.E., Xu, Q., Martinez, M.E., Nguyen, S.T., Chase, P.B., and Gomes, A.V. (2016). The Functional significance of the last 5 residues of the C-terminus of cardiac troponin I. Arch. Biochem. Biophys. pii: S0003-9861(16)30042-X. doi: 10.1016/j.abb.2016.02.023 (in Press).Suche in Google Scholar PubMed PubMed Central

Gomes, A.V., Harada, K., and Potter, J.D. (2005). A mutation in the N-terminus of troponin I that is associated with hypertrophic cardiomyopathy affects the Ca²⁺-sensitivity, phosphorylation kinetics and proteolytic susceptibility of troponin. J. Mol. Cell. Cardiol. 39, 754–765.10.1016/j.yjmcc.2005.05.013Suche in Google Scholar PubMed

Habchi, J., Tompa, P., Longhi, S., and Uversky, V.N. (2014). Introducing protein intrinsic disorder. Chem. Rev. 114, 6561–6588.10.1021/cr400514hSuche in Google Scholar PubMed

Haynes, C., Oldfield, C.J., Ji, F., Klitgord, N., Cusick, M.E., Radivojac, P., Uversky, V.N., Vidal, M., and Iakoucheva, L.M. (2006). Intrinsic disorder is a common feature of hub proteins from four eukaryotic interactomes. PLoS Comput. Biol. 2, e100.10.1371/journal.pcbi.0020100Suche in Google Scholar PubMed PubMed Central

Hensley, N., Dietrich, J., Nyhan, D., Mitter, N., Yee, M.S., and Brady, M. (2015). Hypertrophic cardiomyopathy: a review. Anesth. Analg. 120, 554–569.10.1213/ANE.0000000000000538Suche in Google Scholar PubMed

Hershberger, R.E., Morales, A., and Siegfried, J.D. (2010). Clinical and genetic issues in dilated cardiomyopathy: a review for genetics professionals. Genet. Med. 12, 655–667.10.1097/GIM.0b013e3181f2481fSuche in Google Scholar

Hershberger, R.E., Hedges, D.J., and Morales, A. (2013). Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nat. Rev. Cardiol. 10, 531–547.10.1038/nrcardio.2013.105Suche in Google Scholar

Hoffman, R.M. and Sykes, B.D. (2008). Isoform-specific variation in the intrinsic disorder of troponin I. Proteins 73, 338–350.10.1002/prot.22063Suche in Google Scholar

Hoffman, R.M., Blumenschein, T.M., and Sykes, B.D. (2006). An interplay between protein disorder and structure confers the Ca2+ regulation of striated muscle. J. Mol. Biol. 361, 625–633.10.1016/j.jmb.2006.06.031Suche in Google Scholar

Hubbard, T., Barker, D., Birney, E., Cameron, G., Chen, Y., Clark, L., Cox, T., Cuff, J., Curwen, V., Down, T., et al. (2002). The Ensembl genome database project. Nucleic Acids Res. 30, 38–41.10.1093/nar/30.1.38Suche in Google Scholar

Hwang, P.M., Cai, F., Pineda-Sanabria, S.E., Corson, D.C., and Sykes, B.D. (2014). The cardiac-specific N-terminal region of troponin I positions the regulatory domain of troponin C. Proc. Natl. Acad. Sci. USA 111, 14412–14417.10.1073/pnas.1410775111Suche in Google Scholar

Iakoucheva, L.M., Brown, C.J., Lawson, J.D., Obradovic, Z., and Dunker, A.K. (2002). Intrinsic disorder in cell-signaling and cancer-associated proteins. J. Mol. Biol. 323, 573–584.10.1016/S0022-2836(02)00969-5Suche in Google Scholar

Iakoucheva, L.M., Radivojac, P., Brown, C.J., O’Connor, T.R., Sikes, J.G., Obradovic, Z., and Dunker, A.K. (2004). The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Res. 32, 1037–1049.10.1093/nar/gkh253Suche in Google Scholar

Ishida, T. and Kinoshita, K. (2007). PrDOS: prediction of disordered protein regions from amino acid sequence. Nucleic Acids Res. 35, W460–W464.10.1093/nar/gkm363Suche in Google Scholar

Jefferies, J.L. and Towbin, J.A. (2010). Dilated cardiomyopathy. Lancet 375, 752–762.10.1016/S0140-6736(09)62023-7Suche in Google Scholar

Jin, J.P. (2016). Evolution, regulation, and function of N-terminal variable region of troponin T: modulation of muscle contractility and beyond. Int. Rev. Cell Mol. Biol. 321, 1–28.10.1016/bs.ircmb.2015.09.002Suche in Google Scholar PubMed

Jin, J.P. and Chong, S.M. (2010). Localization of the two tropomyosin-binding sites of troponin T. Arch. Biochem. Biophys. 500, 144–150.10.1016/j.abb.2010.06.001Suche in Google Scholar PubMed PubMed Central

Julien, O., Mercier, P., Allen, C.N., Fisette, O., Ramos, C.H., Lague, P., Blumenschein, T.M., and Sykes, B.D. (2011). Is there nascent structure in the intrinsically disordered region of troponin I? Proteins 79, 1240–1250.10.1002/prot.22959Suche in Google Scholar PubMed

Kalyva, A., Parthenakis, F.I., Marketou, M.E., Kontaraki, J.E., and Vardas, P.E. (2014). Biochemical characterisation of troponin C mutations causing hypertrophic and dilated cardiomyopathies. J. Muscle Res. Cell Motil. 35, 161–178.10.1007/s10974-014-9382-0Suche in Google Scholar PubMed

Katrukha, I.A. (2013). Human cardiac troponin complex. Structure and functions. Biochemistry (Mosc) 78, 1447–1465.10.1134/S0006297913130063Suche in Google Scholar PubMed

Katrukha, I.A. and Gusev, N.B. (2013). Enigmas of cardiac troponin T phosphorylation. J. Mol. Cell. Cardiol. 65, 156–158.10.1016/j.yjmcc.2013.09.017Suche in Google Scholar PubMed

Kedar, V., McDonough, H., Arya, R., Li, H.H., Rockman, H.A., and Patterson, C. (2004). Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I. Proc. Natl. Acad. Sci. USA 101, 18135–18140.10.1073/pnas.0404341102Suche in Google Scholar PubMed PubMed Central

Kimura, A. (2010). Molecular basis of hereditary cardiomyopathy: abnormalities in calcium sensitivity, stretch response, stress response and beyond. J. Hum. Genet. 55, 81–90.10.1038/jhg.2009.138Suche in Google Scholar PubMed

Kowlessur, D. and Tobacman, L.S. (2010a). Low temperature dynamic mapping reveals unexpected order and disorder in troponin. J. Biol. Chem. 285, 38978–38986.10.1074/jbc.M110.181305Suche in Google Scholar PubMed PubMed Central

Kowlessur, D. and Tobacman, L.S. (2010b). Troponin regulatory function and dynamics revealed by H/D exchange-mass spectrometry. J. Biol. Chem. 285, 2686–2694.10.1074/jbc.M109.062349Suche in Google Scholar PubMed PubMed Central

Kowlessur, D. and Tobacman, L.S. (2012). Significance of troponin dynamics for Ca2+-mediated regulation of contraction and inherited cardiomyopathy. J. Biol. Chem. 287, 42299–42311.10.1074/jbc.M112.423459Suche in Google Scholar

Li, M.X. and Hwang, P.M. (2015). Structure and function of cardiac troponin C (TNNC1): Implications for heart failure, cardiomyopathies, and troponin modulating drugs. Gene 571, 153–166.10.1016/j.gene.2015.07.074Suche in Google Scholar

Li, X., Romero, P., Rani, M., Dunker, A.K., and Obradovic, Z. (1999). Predicting protein disorder for N-, C-, and internal regions. Genome Inform Ser Workshop Genome Inform. 10, 30–40.Suche in Google Scholar

Maron, B.J., Gardin, J.M., Flack, J.M., Gidding, S.S., Kurosaki, T.T., and Bild, D.E. (1995). Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA study. Coronary artery risk development in (Young) adults. Circulation 92, 785–789.10.1161/01.CIR.92.4.785Suche in Google Scholar

Maron, B.J., McKenna, W.J., Danielson, G.K., Kappenberger, L.J., Kuhn, H.J., Seidman, C.E., Shah, P.M., Spencer, W.H., 3rd, Spirito, P., Ten Cate, F.J., et al. (2003). American college of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J. Am. Coll. Cardiol. 42, 1687–1713.10.1016/S0195-668X(03)00479-2Suche in Google Scholar

Maron, B.J., Lesser, J.R., Schiller, N.B., Harris, K.M., Brown, C., and Rehm, H.L. (2009). Implications of hypertrophic cardiomyopathy transmitted by sperm donation. J. Am. Med. Assoc. 302, 1681–1684.10.1001/jama.2009.1507Suche in Google Scholar PubMed

Maron, B.J., Ommen, S.R., Semsarian, C., Spirito, P., Olivotto, I., and Maron, M.S. (2014). Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine. J. Am. Coll. Cardiol. 64, 83–99.10.1016/j.jacc.2014.05.003Suche in Google Scholar PubMed

Marston, S.B. and Walker, J.W. (2009). Back to the future: new techniques show that forgotten phosphorylation sites are present in contractile proteins of the heart whilst intensively studied sites appear to be absent. J. Muscle Res. Cell Motil. 30, 93–95.10.1007/s10974-009-9184-ySuche in Google Scholar PubMed PubMed Central

McNally, E.M., Golbus, J.R., and Puckelwartz, M.J. (2013). Genetic mutations and mechanisms in dilated cardiomyopathy. J. Clin. Invest. 123, 19–26.10.1172/JCI62862Suche in Google Scholar PubMed PubMed Central

Messer, A.E. and Marston, S.B. (2014). Investigating the role of uncoupling of troponin I phosphorylation from changes in myofibrillar Ca²⁺-sensitivity in the pathogenesis of cardiomyopathy. Front. Physiol. 5, 315.10.3389/fphys.2014.00315Suche in Google Scholar PubMed PubMed Central

Meszaros, B., Simon, I., and Dosztanyi, Z. (2009). Prediction of protein binding regions in disordered proteins. PLoS Comput. Biol. 5, e1000376.10.1371/journal.pcbi.1000376Suche in Google Scholar PubMed PubMed Central

Metallo, S.J. (2010). Intrinsically disordered proteins are potential drug targets. Curr. Opin. Chem. Biol. 14, 481–488.10.1016/j.cbpa.2010.06.169Suche in Google Scholar PubMed PubMed Central

Oates, M.E., Romero, P., Ishida, T., Ghalwash, M., Mizianty, M.J., Xue, B., Dosztanyi, Z., Uversky, V.N., Obradovic, Z., Kurgan, L., et al. (2013). D²P²: database of disordered protein predictions. Nucleic Acids Res. 41, D508–D516.10.1093/nar/gks1226Suche in Google Scholar PubMed PubMed Central

Obradovic, Z., Peng, K., Vucetic, S., Radivojac, P., and Dunker, A.K. (2005). Exploiting heterogeneous sequence properties improves prediction of protein disorder. Proteins 61 (Suppl 7), 176–182.10.1002/prot.20735Suche in Google Scholar PubMed

Oldfield, C.J. and Dunker, A.K. (2014). Intrinsically disordered proteins and intrinsically disordered protein regions. Annu. Rev. Biochem. 83, 553–584.10.1146/annurev-biochem-072711-164947Suche in Google Scholar PubMed

Oldfield, C.J., Cheng, Y., Cortese, M.S., Romero, P., Uversky, V.N., and Dunker, A.K. (2005). Coupled folding and binding with alpha-helix-forming molecular recognition elements. Biochemistry 44, 12454–12470.10.1021/bi050736eSuche in Google Scholar PubMed

Oldfield, C.J., Meng, J., Yang, J.Y., Yang, M.Q., Uversky, V.N., and Dunker, A.K. (2008). Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners. BMC Genomics 9(Suppl 1), S1.10.1186/1471-2164-9-S1-S1Suche in Google Scholar PubMed PubMed Central

Patil, A. and Nakamura, H. (2006). Disordered domains and high surface charge confer hubs with the ability to interact with multiple proteins in interaction networks. FEBS Lett. 580, 2041–2045.10.1016/j.febslet.2006.03.003Suche in Google Scholar PubMed

Pejaver, V., Hsu, W.L., Xin, F., Dunker, A.K., Uversky, V.N., and Radivojac, P. (2014). The structural and functional signatures of proteins that undergo multiple events of post-translational modification. Protein Sci. 23, 1077–1093.10.1002/pro.2494Suche in Google Scholar PubMed PubMed Central

Peng, Z. and Kurgan, L. (2015). High-throughput prediction of RNA, DNA and protein binding regions mediated by intrinsic disorder. Nucleic Acids Res. 43, e121.10.1093/nar/gkv585Suche in Google Scholar PubMed PubMed Central

Peng, K., Vucetic, S., Radivojac, P., Brown, C.J., Dunker, A.K., and Obradovic, Z. (2005). Optimizing long intrinsic disorder predictors with protein evolutionary information. J. Bioinform. Comput. Biol. 3, 35–60.10.1142/S0219720005000886Suche in Google Scholar PubMed

Peng, K., Radivojac, P., Vucetic, S., Dunker, A.K., and Obradovic, Z. (2006). Length-dependent prediction of protein intrinsic disorder. BMC Bioinf. 7, 208.10.1186/1471-2105-7-208Suche in Google Scholar

Peng, Y., Ayaz-Guner, S., Yu, D., and Ge, Y. (2014). Top-down mass spectrometry of cardiac myofilament proteins in health and disease. Proteomics Clin. Appl. 8, 554–568.10.1002/prca.201400043Suche in Google Scholar

Perry, S.V. (1998). Troponin T: genetics, properties and function. J. Muscle Res. Cell Motil. 19, 575–602.10.1023/A:1005397501968Suche in Google Scholar

Pinto, J.R., Siegfried, J.D., Parvatiyar, M.S., Li, D., Norton, N., Jones, M.A., Liang, J., Potter, J.D., Hershberger, R.E. (2011). Functional characterization of TNNC1 rare variants identified in dilated cardiomyopathy. J. Biol. Chem. 286, 34404–34412.10.1074/jbc.M111.267211Suche in Google Scholar

Radivojac, P., Iakoucheva, L.M., Oldfield, C.J., Obradovic, Z., Uversky, V.N., and Dunker, A.K. (2007). Intrinsic disorder and functional proteomics. Biophys. J. 92, 1439–1456.10.1529/biophysj.106.094045Suche in Google Scholar

Richard, P., Charron, P., Carrier, L., Ledeuil, C., Cheav, T., Pichereau, C., Benaiche, A., Isnard, R., Dubourg, O., Burban, M., et al. (2003). Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation 107, 2227–2232.10.1161/01.CIR.0000066323.15244.54Suche in Google Scholar

Romero, P., Obradovic, Z., Li, X., Garner, E.C., Brown, C.J., and Dunker, A.K. (2001). Sequence complexity of disordered protein. Proteins 42, 38–48.10.1002/1097-0134(20010101)42:1<38::AID-PROT50>3.0.CO;2-3Suche in Google Scholar

Rowland, T. (2009). Sudden unexpected death in young athletes: reconsidering “hypertrophic cardiomyopathy”. Pediatrics 123, 1217–1222.10.1542/peds.2008-0708Suche in Google Scholar

Russell, R.B. and Gibson, T.J. (2008). A careful disorderliness in the proteome: sites for interaction and targets for future therapies. FEBS Lett. 582, 1271–1275.10.1016/j.febslet.2008.02.027Suche in Google Scholar

Sancho Solis, R., Ge, Y., and Walker, J.W. (2008). Single amino acid sequence polymorphisms in rat cardiac troponin revealed by top-down tandem mass spectrometry. J. Muscle Res. Cell Motil. 29, 203–212.10.1007/s10974-009-9168-ySuche in Google Scholar

Semsarian, C., Ingles, J., Maron, M.S., and Maron, B.J. (2015). New perspectives on the prevalence of hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 65, 1249–1254.10.1016/j.jacc.2015.01.019Suche in Google Scholar

Singh, G.P., Ganapathi, M., Sandhu, K.S., and Dash, D. (2006). Intrinsic unstructuredness and abundance of PEST motifs in eukaryotic proteomes. Proteins 62, 309–315.10.1002/prot.20746Suche in Google Scholar

Steward, R.E., MacArthur, M.W., Laskowski, R.A., and Thornton, J.M. (2003). Molecular basis of inherited diseases: a structural perspective. Trends Genet. 19, 505–513.10.1016/S0168-9525(03)00195-1Suche in Google Scholar

Streng, A.S., de Boer, D., van der Velden, J., van Dieijen-Visser, M.P., and Wodzig, W.K.W.H. (2013). Posttranslational modifications of cardiac troponin T: an overview. J. Mol. Cell. Cardiol. 63, 47–56.10.1016/j.yjmcc.2013.07.004Suche in Google Scholar

Sturm, A.C. (2013). Genetic testing in the contemporary diagnosis of cardiomyopathy. Curr. Heart Fail Rep. 10, 63–72.10.1007/s11897-012-0124-6Suche in Google Scholar

Szklarczyk, D., Franceschini, A., Kuhn, M., Simonovic, M., Roth, A., Minguez, P., Doerks, T., Stark, M., Muller, J., Bork, P., et al. (2011). The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 39, D561–D568.10.1093/nar/gkq973Suche in Google Scholar

Takeda, S., Yamashita, A., Maeda, K., and Maeda, Y. (2003). Structure of the core domain of human cardiac troponin in the Ca²⁺-saturated form. Nature 424, 35–41.10.1038/nature01780Suche in Google Scholar

Tompa, P. (2002). Intrinsically unstructured proteins. Trends Biochem. Sci. 27, 527–533.10.1016/S0968-0004(02)02169-2Suche in Google Scholar

Tompa, P. (2005). The interplay between structure and function in intrinsically unstructured proteins. FEBS Lett. 579, 3346–3354.10.1016/j.febslet.2005.03.072Suche in Google Scholar PubMed

Tompa, P. (2012). Intrinsically disordered proteins: a 10-year recap. Trends Biochem. Sci. 37, 509–516.10.1016/j.tibs.2012.08.004Suche in Google Scholar PubMed

Tompa, P. and Csermely, P. (2004). The role of structural disorder in the function of RNA and protein chaperones. FASEB J. 18, 1169–1175.10.1096/fj.04-1584revSuche in Google Scholar PubMed

Tompa, P. and Fuxreiter, M. (2008). Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions. Trends Biochem. Sci. 33, 2–8.10.1016/j.tibs.2007.10.003Suche in Google Scholar PubMed

Tompa, P., Szasz, C., and Buday, L. (2005). Structural disorder throws new light on moonlighting. Trends Biochem. Sci. 30, 484–489.10.1016/j.tibs.2005.07.008Suche in Google Scholar PubMed

Tompa, P., Fuxreiter, M., Oldfield, C.J., Simon, I., Dunker, A.K., and Uversky, V.N. (2009). Close encounters of the third kind: disordered domains and the interactions of proteins. Bioessays 31, 328–335.10.1002/bies.200800151Suche in Google Scholar PubMed

Towbin, J.A., Lowe, A.M., Colan, S.D., Sleeper, L.A., Orav, E.J., Clunie, S., Messere, J., Cox, G.F., Lurie, P.R., Hsu, D., et al. (2006). Incidence, causes, and outcomes of dilated cardiomyopathy in children. J. Am. Med. Assoc. 296, 1867–1876.10.1001/jama.296.15.1867Suche in Google Scholar PubMed

Uversky, V.N. (2002a). Natively unfolded proteins: a point where biology waits for physics. Protein Sci. 11, 739–756.10.1110/ps.4210102Suche in Google Scholar PubMed PubMed Central

Uversky, V.N. (2002b). What does it mean to be natively unfolded? Eur. J. Biochem. 269, 2–12.10.1046/j.0014-2956.2001.02649.xSuche in Google Scholar PubMed

Uversky, V.N. (2003). Protein folding revisited. A polypeptide chain at the folding-misfolding-nonfolding cross-roads: which way to go? Cell. Mol. Life Sci. 60, 1852–1871.10.1007/s00018-003-3096-6Suche in Google Scholar PubMed

Uversky, V.N. (2010). The mysterious unfoldome: structureless, underappreciated, yet vital part of any given proteome. J. Biomed. Biotechnol. 2010, 568068.10.1155/2010/568068Suche in Google Scholar PubMed PubMed Central

Uversky, V.N. (2011). Multitude of binding modes attainable by intrinsically disordered proteins: a portrait gallery of disorder-based complexes. Chem. Soc. Rev. 40, 1623–1634.10.1039/C0CS00057DSuche in Google Scholar PubMed

Uversky, V.N. (2012). Intrinsically disordered proteins and novel strategies for drug discovery. Expert Opin. Drug Discov. 7, 475–488.10.1517/17460441.2012.686489Suche in Google Scholar

Uversky, V.N. (2013a). Intrinsic disorder-based protein interactions and their modulators. Curr. Pharm. Des. 19, 4191–4213.10.2174/1381612811319230005Suche in Google Scholar

Uversky, V.N. (2013b). Unusual biophysics of intrinsically disordered proteins. Biochim. Biophys. Acta 1834, 932–951.10.1016/j.bbapap.2012.12.008Suche in Google Scholar

Uversky, V.N. (2015). The multifaceted roles of intrinsic disorder in protein complexes. FEBS Lett. 589, 2498–2506.10.1016/j.febslet.2015.06.004Suche in Google Scholar

Uversky, V.N. and Dunker, A.K. (2008). Biochemistry. Controlled chaos. Science 322, 1340–1341.Suche in Google Scholar

Uversky, V.N. and Dunker, A.K. (2010). Understanding protein non-folding. Biochim. Biophys. Acta 1804, 1231–1264.10.1016/j.bbapap.2010.01.017Suche in Google Scholar

Uversky, V.N., Gillespie, J.R., and Fink, A.L. (2000). Why are “natively unfolded” proteins unstructured under physiologic conditions? Proteins 41, 415–427.10.1002/1097-0134(20001115)41:3<415::AID-PROT130>3.0.CO;2-7Suche in Google Scholar

Uversky, V.N., Oldfield, C.J., and Dunker, A.K. (2005). Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling. J. Mol. Recognit. 18, 343–384.10.1002/jmr.747Suche in Google Scholar

Uversky, V.N., Oldfield, C.J., and Dunker, A.K. (2008). Intrinsically disordered proteins in human diseases: introducing the D2 concept. Annu. Rev. Biophys. 37, 215–246.10.1146/annurev.biophys.37.032807.125924Suche in Google Scholar

Uversky, V.N., Oldfield, C.J., Midic, U., Xie, H., Xue, B., Vucetic, S., Iakoucheva, L.M., Obradovic, Z., and Dunker, A.K. (2009). Unfoldomics of human diseases: linking protein intrinsic disorder with diseases. BMC Genomics 10(Suppl. 1), S7.10.1186/1471-2164-10-S1-S7Suche in Google Scholar

Uversky, V.N., Dave, V., Iakoucheva, L.M., Malaney, P., Metallo, S.J., Pathak, R.R., and Joerger, A.C. (2014). Pathological unfoldomics of uncontrolled chaos: intrinsically disordered proteins and human diseases. Chem. Rev. 114, 6844–6879.10.1021/cr400713rSuche in Google Scholar

Vacic, V., Markwick, P.R., Oldfield, C.J., Zhao, X., Haynes, C., Uversky, V.N., and Iakoucheva, L.M. (2012). Disease-associated mutations disrupt functionally important regions of intrinsic protein disorder. PLoS Comput. Biol. 8, e1002709.10.1371/journal.pcbi.1002709Suche in Google Scholar PubMed PubMed Central

van der Lee, R., Buljan, M., Lang, B., Weatheritt, R.J., Daughdrill, G.W., Dunker, A.K., Fuxreiter, M., Gough, J., Gsponer, J., Jones, D.T., et al. (2014). Classification of intrinsically disordered regions and proteins. Chem. Rev. 114, 6589–6631.10.1021/cr400525mSuche in Google Scholar PubMed PubMed Central

Vitkup, D., Sander, C., and Church, G.M. (2003). The amino-acid mutational spectrum of human genetic disease. Genome Biol. 4, R72.10.1186/gb-2003-4-11-r72Suche in Google Scholar PubMed PubMed Central

Vucetic, S., Xie, H., Iakoucheva, L.M., Oldfield, C.J., Dunker, A.K., Obradovic, Z., and Uversky, V.N. (2007). Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions. J. Proteome Res. 6, 1899–1916.10.1021/pr060393mSuche in Google Scholar PubMed PubMed Central

Walsh, I., Martin, A.J., Di Domenico, T., and Tosatto, S.C. (2012). ESpritz: accurate and fast prediction of protein disorder. Bioinformatics 28, 503–509.10.1093/bioinformatics/btr682Suche in Google Scholar PubMed

Wang, Y., Pinto, J.R., Solis, R.S., Dweck, D., Liang, J., Diaz-Perez, Z., Ge, Y., Walker, J.W., and Potter, J.D. (2012). Generation and functional characterization of knock-in mice harboring the cardiac troponin I-R21C mutation associated with hypertrophic cardiomyopathy. J. Biol. Chem. 287, 2156–2167.10.1074/jbc.M111.294306Suche in Google Scholar PubMed PubMed Central

Ward, J.J., Sodhi, J.S., McGuffin, L.J., Buxton, B.F., and Jones, D.T. (2004). Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J. Mol. Biol. 337, 635–645.10.1016/j.jmb.2004.02.002Suche in Google Scholar PubMed

Wei, B. and Jin, J.P. (2016). TNNT1, TNNT2, and TNNT3: Isoform genes, regulation, and structure-function relationships. Gene 582, 1–13.10.1016/j.gene.2016.01.006Suche in Google Scholar PubMed PubMed Central

Wigle, E.D., Rakowski, H., Kimball, B.P., and Williams, W.G. (1995). Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation 92, 1680–1692.10.1161/01.CIR.92.7.1680Suche in Google Scholar PubMed

Willott, R.H., Gomes, A.V., Chang, A.N., Parvatiyar, M.S., Pinto, J.R., and Potter, J.D. (2010). Mutations in Troponin that cause HCM, DCM AND RCM: what can we learn about thin filament function? J. Mol. Cell. Cardiol. 48, 882–892.10.1016/j.yjmcc.2009.10.031Suche in Google Scholar PubMed

Witt, S.H., Granzier, H., Witt, C.C., and Labeit, S. (2005). MURF-1 and MURF-2 target a specific subset of myofibrillar proteins redundantly: towards understanding MURF-dependent muscle ubiquitination. J. Mol. Biol. 350, 713–722.10.1016/j.jmb.2005.05.021Suche in Google Scholar PubMed

Wright, P.E. and Dyson, H.J. (1999). Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J. Mol. Biol. 293, 321–331.10.1006/jmbi.1999.3110Suche in Google Scholar PubMed

Wright, P.E. and Dyson, H.J. (2009). Linking folding and binding. Curr. Opin. Struct. Biol. 19, 31–38.10.1016/j.sbi.2008.12.003Suche in Google Scholar PubMed PubMed Central

Xia, J., Han, L., and Zhao, Z. (2012). Investigating the relationship of DNA methylation with mutation rate and allele frequency in the human genome. BMC Genomics 13(Suppl 8), S7.10.1186/1471-2164-13-S8-S7Suche in Google Scholar PubMed PubMed Central

Xie, H., Vucetic, S., Iakoucheva, L.M., Oldfield, C.J., Dunker, A.K., Obradovic, Z., and Uversky, V.N. (2007a). Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins. J. Proteome Res. 6, 1917–1932.10.1021/pr060394eSuche in Google Scholar PubMed PubMed Central

Xie, H., Vucetic, S., Iakoucheva, L.M., Oldfield, C.J., Dunker, A.K., Uversky, V.N., and Obradovic, Z. (2007b). Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 6, 1882–1898.10.1021/pr060392uSuche in Google Scholar PubMed PubMed Central

Xue, B., Dunbrack, R.L., Williams, R.W., Dunker, A.K., and Uversky, V.N. (2010). PONDR-FIT: a meta-predictor of intrinsically disordered amino acids. Biochim. Biophys. Acta 1804, 996–1010.10.1016/j.bbapap.2010.01.011Suche in Google Scholar PubMed PubMed Central

Zabrouskov, V., Ge, Y., Schwartz, J., and Walker, J.W. (2008). Unraveling molecular complexity of phosphorylated human cardiac troponin I by top down electron capture dissociation/electron transfer dissociation mass spectrometry. Mol. Cell. Proteomics 7, 1838–1849.10.1074/mcp.M700524-MCP200Suche in Google Scholar PubMed

Zhang, J., Dong, X., Hacker, T.A., and Ge, Y. (2010). Deciphering modifications in swine cardiac troponin I by top-down high-resolution tandem mass spectrometry. J. Am. Soc. Mass Spectrom. 21, 940–948.10.1016/j.jasms.2010.02.005Suche in Google Scholar PubMed PubMed Central

Zhang, J., Zhang, H., Ayaz-Guner, S., Chen, Y.C., Dong, X., Xu, Q., and Ge, Y. (2011). Phosphorylation, but not alternative splicing or proteolytic degradation, is conserved in human and mouse cardiac troponin T. Biochemistry 50, 6081–6092.10.1021/bi2006256Suche in Google Scholar PubMed PubMed Central

Zhang, P., Kirk, J.A., Ji, W., dos Remedios, C.G., Kass, D.A., Van Eyk, J.E., and Murphy, A.M. (2012). Multiple reaction monitoring to identify site-specific troponin I phosphorylated residues in the failing human heart. Circulation 126, 1828–1837.10.1161/CIRCULATIONAHA.112.096388Suche in Google Scholar PubMed PubMed Central