Journal article
Systematic analysis of tropomodulin/tropomyosin interactions uncovers fine-tuned binding specificity of intrinsically disordered proteins
Journal of molecular recognition, Vol.24(4), pp.647-655
07/2011
Handle:
https://hdl.handle.net/2376/101056
PMID: 21584876
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.
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Details
- Title
- Systematic analysis of tropomodulin/tropomyosin interactions uncovers fine-tuned binding specificity of intrinsically disordered proteins
- Creators
- Vladimir N Uversky - Department of Biochemistry and Molecular Biology, Institute for Intrinsically Disordered Protein Research, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. vuversky@iupui.eduSamar P ShahYulia GritsynaSarah E Hitchcock-DeGregoriAlla S Kostyukova
- Publication Details
- Journal of molecular recognition, Vol.24(4), pp.647-655
- Academic Unit
- Chemical Engineering and Bioengineering, School of
- Publisher
- England
- Grant note
- R01 GM081688 / NIGMS NIH HHS GM081688 / NIGMS NIH HHS
- Identifiers
- 99900546666801842
- Language
- English
- Resource Type
- Journal article