Systematic Analysis of Tropomodulin/tropomyosin Interactions Uncovers Fine-tuned Binding Specificity of Intrinsically Disordered Proteins
Document Type
Article
Publication Date
2011
Digital Object Identifier (DOI)
https://doi.org/10.1002/jmr.1093
Abstract
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.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Journal of Molecular Recognition, v. 24, issue 4, p. 647-655
Scholar Commons Citation
Uversky, Vladimir N.; Shah, Samar P.; Gritsyna, Yulia; Hitchcock-DeGregori, Sarah E.; and Kostyukova, Alla S., "Systematic Analysis of Tropomodulin/tropomyosin Interactions Uncovers Fine-tuned Binding Specificity of Intrinsically Disordered Proteins" (2011). Molecular Medicine Faculty Publications. 480.
https://digitalcommons.usf.edu/mme_facpub/480
