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Biophysical and biochemical analysis of hnRNP K: arginine methylation, reversible aggregation and combinatorial binding to nucleic acids

  • Bodo Moritz , Hauke Lilie , Isabel S. Naarmann-de Vries , Henning Urlaub , Elmar Wahle , Antje Ostareck-Lederer and Dirk H. Ostareck EMAIL logo
Published/Copyright: July 8, 2014
Biological Chemistry
From the journal Biological Chemistry Volume 395 Issue 7-8

Abstract

Analysis of arginine methylation, which affects specific protein interactions in eukaryotic cells, requires access to methylated protein for biophysical and biochemical studies. Methylation of heterogeneous nuclear ribonucleoprotein K (hnRNP K) upon co-expression with protein arginine methyltransferase 1 in E. coli was monitored by mass spectrometry and found to be identical to the modification of hnRNP K purified from mammalian cells. Recombinant non-methylated and arginine-methylated hnRNP K (MethnRNP K) were used to characterize self-aggregation and nucleic acid binding. Analytical ultracentrifugation and static light scattering experiments revealed that hnRNP K methylation does not impact reversible self-aggregation, which can be prevented by high ionic strength and organic additives. Filter binding assays were used to compare the binding of non-methylated and MethnRNP K to the pyrimidine repeat-containing differentiation control element (DICE) of reticulocyte 15-lipoxygenase mRNA 3′ UTR. No affinity differences were detected for both hnRNP K variants. A series of oligonucleotides carrying various numbers of C4 motifs at different positions was used in steady state competition assays with fluorescently-labeled functional differentiation control element (2R). Quantitative evaluation indicated that all hnRNP K homology domains of hnRNP K contribute differentially to RNA binding, with KH1–KH2 acting as a tandem domain and KH3 as an individual binding domain.

Keywords: arginine methylation; heterogeneous nuclear ribonucleoprotein K; hnRNP K homology domains; RNA-binding domain; self-aggregation; steady state nucleic acid-interaction
Corresponding author: Dirk H. Ostareck, Department of Intensive Care and Intermediate Care, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany, e-mail:

Acknowledgments

We are grateful to Michael Spinka for critical discussions on association equilibria and advice on SigmaPlot® analysis. Special thanks to all members of the GRK 1026 for critical discussions and advice. We acknowledge X. Cheng for providing pET28b-PRMT1. We thank Nadine Simons for technical assistance. Funding was provided by the DFG to D.H.O. (GRK 1026); to A.O.-L. (OS 290/1-1, 1-2 and OS 290/2-1, 2-2); and to E.W. (SFB 610).

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Supplemental Material: The online version of this article (DOI 10.1515/hsz-2014-0146) offers supplementary material, available to authorized users.

Received: 2014-2-17
Accepted: 2014-5-20
Published Online: 2014-7-8
Published in Print: 2014-7-1

©2014 by Walter de Gruyter Berlin/Boston

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  16. Biophysical and biochemical analysis of hnRNP K: arginine methylation, reversible aggregation and combinatorial binding to nucleic acids
  17. An ancient oxidoreductase making differential use of its cofactors
  18. Biophysical characterization of polyomavirus minor capsid proteins
  19. Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A
  20. Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues
  21. Thermodynamic signatures in macromolecular interactions involving conformational flexibility
https://doi.org/10.1515/hsz-2014-0146
Keywords for this article
arginine methylation; heterogeneous nuclear ribonucleoprotein K; hnRNP K homology domains; RNA-binding domain; self-aggregation; steady state nucleic acid-interaction

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: conformational transitions in macromolecular interactions
  4. Single-molecule spectroscopy of unfolded proteins and chaperonin action
  5. Influence of the polypeptide environment next to amyloidogenic peptides on fibril formation
  6. Structure of large dsDNA viruses
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  9. Structural insights into calmodulin/Munc13 interaction
  10. Interaction of linear polyamines with negatively charged phospholipids: the effect of polyamine charge distance
  11. Interaction of the human N-Ras protein with lipid raft model membranes of varying degrees of complexity
  12. Lanthanides as substitutes for calcium ions in the activation of plant α-type phospholipase D
  13. Insights from reconstitution reactions of COPII vesicle formation using pure components and low mechanical perturbation
  14. Identification of key residues in the formate channel FocA that control import and export of formate
  15. Twin-arginine translocation-arresting protein regions contact TatA and TatB
  16. Biophysical and biochemical analysis of hnRNP K: arginine methylation, reversible aggregation and combinatorial binding to nucleic acids
  17. An ancient oxidoreductase making differential use of its cofactors
  18. Biophysical characterization of polyomavirus minor capsid proteins
  19. Structural basis for PTPA interaction with the invariant C-terminal tail of PP2A
  20. Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues
  21. Thermodynamic signatures in macromolecular interactions involving conformational flexibility
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