Startseite Human septin isoforms and the GDP-GTP cycle
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Human septin isoforms and the GDP-GTP cycle

  • Eldar Zent und Alfred Wittinghofer EMAIL logo
Veröffentlicht/Copyright: 18. November 2013

Abstract

Septins form oligomeric complexes consisting of septins from different subgroups, which form filaments that are involved in a number of biological processes. They are GTP-binding proteins that contain all the necessary elements to perform the general GDP-to-GTP conformational switch. It is however unclear whether or not such a switch is important for the dynamics of septin filaments. Here we investigate the complex GTPase reaction of members of each of the four human septin groups, which is dominated by the stability of dimer formation via the nucleotide binding or so-called G-interface. The results also show that the actual hydrolysis reaction is very similar for three septin groups in the monomeric state while the Sept6 has no GTPase activity. Sept7, the only member of the Sept7 subgroup, forms a very tight G-interface dimer in the GDP-bound state. Here we show that the stability of the interface is dramatically decreased by exchanging GDP with a nucleoside triphosphate, which is believed to influence filament formation and dynamics via Sept7.


Corresponding author: Alfred Wittinghofer, Structural Biology Group, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 14, 44227 Dortmund, Germany, e-mail:

References

Bertin, A., McMurray, M.A., Grob, P., Park, S.S., Garcia, G. 3rd, Patanwala, I., Ng, H.I., Alber, T., Thorner, J., and Nogales, E. (2008). Saccharomyces cerevisiae septins: supramolecular organization of heterooligomers and the mechanism of filament assembly. Proc. Natl. Acad. Sci. USA 105, 8274–8279.10.1073/pnas.0803330105Suche in Google Scholar PubMed PubMed Central

Bertin, A., McMurray, M.A., Thai, L., Garcia, G. 3rd, Votin, V., Grob, P., Allyn, T., Thorner, J., and Nogales, E. (2010). Phosphatidylinositol-4,5-bisphosphate promotes budding yeast septin filament assembly and organization. J. Mol. Biol. 404, 711–731.10.1016/j.jmb.2010.10.002Suche in Google Scholar PubMed PubMed Central

Bowne-Anderson, H., Zanic, M., Kauer, M., and Howard, J. (2013). Microtubule dynamic instability: a new model with coupled GTP hydrolysis and multistep catastrophe. Bioessays 35, 452–461.10.1002/bies.201200131Suche in Google Scholar PubMed PubMed Central

Farkasovsky, M., Herter, P., Voss, B., and Wittinghofer, A. (2005). Nucleotide binding and filament assembly of recombinant yeast septin complexes. Biol. Chem. 386, 643–656.10.1515/BC.2005.075Suche in Google Scholar PubMed

Field, C.M., al-Awar, O., Rosenblatt, J., Wonq, M.L., Alberts, B., and Mitchison, T.J. (1996). A purified Drosophila septin complex forms filaments and exhibits GTPase activity. J. Cell Biol. 133, 605–616.10.1083/jcb.133.3.605Suche in Google Scholar PubMed PubMed Central

Gasper, R., Meyer, S., Gotthardt, K., Sirajuddin, M., and Wittinghofer, A. (2009). It takes two to tango: regulation of G proteins by dimerization. Nat. Rev. Mol. Cell. Biol. 10, 423–429.10.1038/nrm2689Suche in Google Scholar PubMed

Huang, Y.W., Surka, M.C., Reynaud, D., Pace-Asciak, C., and Trimble, W.S. (2006). GTP binding and hydrolysis kinetics of human septin 2. FEBS J. 273, 3248–3260.10.1111/j.1742-4658.2006.05333.xSuche in Google Scholar PubMed

John, C.M., Hite, R.K., Weirich, C.S., Fitzgerald, D.J., Jawhari, H., Faty, M., Schläpfer, D., Kroschewski, R., Winkler, F.K., Walz, T., et al. (2007). The Caenorhabditis elegance septin complex is nonpolar. EMBO 26, 3296–3307.10.1038/sj.emboj.7601775Suche in Google Scholar PubMed PubMed Central

Kinoshita, M. (2003). Assebly of mammalian septins. J. Biochem. 134, 491–496.10.1093/jb/mvg182Suche in Google Scholar PubMed

Kudryashov, D.S. and Reisler, E. (2013). ATP and ADP actin states. Biopolymers 99, 245–256.10.1002/bip.22155Suche in Google Scholar PubMed PubMed Central

Lin, C.W. and Ting, A.Y. (2006) Transglutaminase-catalyzed site-specific conjugation of small-molecule probes to proteins in vitro and on the surface of living cells. J. Am. Chem. Soc. 128, 4542–4543.10.1021/ja0604111Suche in Google Scholar PubMed PubMed Central

Macedo, J.N., Valadares, N.F., Marques, I.A., Ferreira, F.M., Damalio, J.C., Pereira, H.M., Garratt, R.C., and Araujo, A.P. (2013). The structure and properties of septin 3: a possible missing link in septin filament formation. Biochem. J. 450, 95–105.10.1042/BJ20120851Suche in Google Scholar PubMed

Nakahira, M., Macedo, J.N.A., Seraphim, T.V., Cavalcante, N., Souza, T.A.C.B., Damalio, J.C.P., Reyes, L.F., Assmann, E.M., Alborghetti, M.R., Garratt, R.C., et al. (2011). A Draft of the human septin interactome. PLoS ONE 5, e13799.10.1371/journal.pone.0013799Suche in Google Scholar

Pan, F., Malmberg, R.L., and Momany, M. (2007). Analysis of septins across kingdoms revelas orthology and new motifs. BMC Evol. Biol. 7, 103.10.1186/1471-2148-7-103Suche in Google Scholar PubMed PubMed Central

Sandrock, K., Bartsch, I., Bläser, S., Busse, A., Busse, E., and Zieger, B. (2011). Characterization of human septin interactions. Biol. Chem. 392, 751–761.10.1515/BC.2011.081Suche in Google Scholar PubMed

Sirajuddin, M., Farkasovsky, M., Hauer, F., Kühlmann, D., Macara, I.G., Weyand, M., Stark, H., and Wittinghofer, A. (2007). Structural insight into filament formation by mammalian septins. Nature 449, 311–315.10.1038/nature06052Suche in Google Scholar PubMed

Sirajuddin, M., Farkasovsky, M., Zent, E., and Wittinghofer, A. (2009). GTP-induced conformational changes in septins and implications for function. Proc. Natl. Acad. Sci. USA 106, 16592–16597.10.1073/pnas.0902858106Suche in Google Scholar PubMed PubMed Central

Tucker, J., Sczakiel, G., Feuerstein, J., John, J., Goody, R.S., and Wittinghofer, A. (1986). Expression of p21 proteins in Escherichia Coli and steriochemistry of the nucleotide-binding site. EMBO J. 5, 1351–1358.10.1002/j.1460-2075.1986.tb04366.xSuche in Google Scholar

Versele, M. and Thorner J. (2004). Septin collar formation in budding yeast requires GTP binding and direct phosphorylation by the PAK, Cla4. J. Cell Biol. 164, 701–715.10.1083/jcb.200312070Suche in Google Scholar PubMed PubMed Central

Vetter IR. and Wittinghofer, A. (2001). The guanine nucleotide-binding switch in three dimensions. Science 294, 1299–1304.10.1126/science.1062023Suche in Google Scholar PubMed

Weirich, C.S., Erzberger, J.P., and Barral, Y. (2008). The septin family of GTPases: architecture and dynamics. Nat. Rev. Mol. Cell. Biol. 9, 478–489.10.1038/nrm2407Suche in Google Scholar PubMed

Zent E., Vetter IR., and Wittinghofer, A. (2011). Structural and biochemical properties of Sept7, a unique septin required for filament formation. Biol. Chem. 392, 791–797.10.1515/BC.2011.082Suche in Google Scholar PubMed

Received: 2013-10-22
Accepted: 2013-11-14
Published Online: 2013-11-18
Published in Print: 2014-02-01

©2014 by Walter de Gruyter Berlin Boston

Heruntergeladen am 22.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2013-0268/html
Button zum nach oben scrollen