These authors contributed equally.
Systematic analysis of tropomodulin/tropomyosin interactions uncovers fine-tuned binding specificity of intrinsically disordered proteins
Article first published online: 17 MAY 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Journal of Molecular Recognition
Volume 24, Issue 4, pages 647–655, July/August 2011
How to Cite
Uversky, V. N., Shah, S. P., Gritsyna, Y., Hitchcock-DeGregori, S. E. and Kostyukova, A. S. (2011), Systematic analysis of tropomodulin/tropomyosin interactions uncovers fine-tuned binding specificity of intrinsically disordered proteins. J. Mol. Recognit., 24: 647–655. doi: 10.1002/jmr.1093
- Issue published online: 7 APR 2011
- Article first published online: 17 MAY 2011
- Manuscript Accepted: 24 AUG 2010
- Manuscript Revised: 23 AUG 2010
- Manuscript Received: 25 JUN 2010
- intrinsically disordered proteins;
- protein–protein interactions;
- circular dichroism
An intriguing regulatory mechanism is the ability of some proteins to recognize their binding partners in an isoform-specific manner. In this study we undertook a systematic analysis of the specificity of the tropomodulin (Tmod) interaction with tropomyosin (TM) to show that affinities of different Tmod isoforms to TM are isoform-dependent. Intrinsic disorder predictions, alignment of sequences, and circular dichroism were utilized to establish a structural basis for these isoform-specific interactions. The affinity of model peptides derived from the N-terminus of different TM isoforms to protein fragments that correspond to the two TM-binding sites of different Tmod isoforms were analyzed. Several residues were determined to be responsible for the isoform-dependent differences in affinity. We suggest that changing a set of residues rather than a single residue is needed to alter the binding affinity of one isoform to mimic the affinity of another isoform. The general intrinsic disorder predictor, PONDR® VLXT, was shown to be a useful tool for analyzing regions involved in isoform-specific binding and for predicting the residues important for isoform differences in binding. Knowing the residues responsible for isoform-specific affinity creates a tool suitable for studying the influence of Tmod/TM interactions on sarcomere assembly in muscle cells or actin dynamics in non-muscle cells. Copyright © 2011 John Wiley & Sons, Ltd.