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Biochem Biophys Res Commun. 2017 Feb 26;484(1):21-26. doi: 10.1016/j.bbrc.2017.01.089. Epub 2017 Jan 19.

Thermodynamic contribution of backbone conformational entropy in the binding between SH3 domain and proline-rich motif.

Author information

1
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
2
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA. Electronic address: jaehyuncho@tamu.edu.

Abstract

Biological functions of intrinsically disordered proteins (IDPs), and proteins containing intrinsically disordered regions (IDRs) are often mediated by short linear motifs, like proline-rich motifs (PRMs). Upon binding to their target proteins, IDPs undergo a disorder-to-order transition which is accompanied by a large conformational entropy penalty. Hence, the molecular mechanisms underlying control of conformational entropy are critical for understanding the binding affinity and selectivity of IDPs-mediated protein-protein interactions (PPIs). Here, we investigated the backbone conformational entropy change accompanied by binding of the N-terminal SH3 domain (nSH3) of CrkII and PRM derived from guanine nucleotide exchange factor 1 (C3G). In particular, we focused on the estimation of conformational entropy change of disordered PRM upon binding to the nSH3 domain. Quantitative characterization of conformational dynamics of disordered peptides like PRMs is limited. Hence, we combined various methods, including NMR model-free analysis, δ2D, DynaMine, and structure-based calculation of entropy loss. This study demonstrates that the contribution of backbone conformational entropy change is significant in the PPIs mediated by IDPs/IDRs.

KEYWORDS:

Conformational entropy; Intrinsically disordered proteins; Proline-rich motif; Protein-protein interactions; SH3 domain

PMID:
28111343
DOI:
10.1016/j.bbrc.2017.01.089
[Indexed for MEDLINE]

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