التفاصيل البيبلوغرافية
| العنوان: |
A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers. |
| المؤلفون: |
Hwang, Theresa1, Parker, Sara S.2, Hill, Samantha M.2, Ilunga, Meucci W.1, Grant, Robert A.1, Mouneimne, Ghassan2, Keating, Amy E.1,3 keating@mit.edu |
| المصدر: |
eLife. 12/2/2021, p1-21. 21p. |
| مصطلحات موضوعية: |
*ACTIN, *BINDING sites, *CILIA & ciliary motion, *CANCER cells |
| مستخلص: |
Metazoan proteomes contain many paralogous proteins that have evolved distinct functions. The Ena/VASP family of actin regulators consists of three members that share an EVH1 interaction domain with a 100% conserved binding site. A proteome- wide screen revealed photoreceptor cilium actin regulator (PCARE) as a high- affinity ligand for ENAH EVH1. Here, we report the surprising observation that PCARE is ~100- fold specific for ENAH over paralogs VASP and EVL and can selectively bind ENAH and inhibit ENAH- dependent adhesion in cells. Specificity arises from a mechanism whereby PCARE stabilizes a conformation of the ENAH EVH1 domain that is inaccessible to family members VASP and EVL. Structure- based modeling rapidly identified seven residues distributed throughout EVL that are sufficient to differentiate binding by ENAH vs. EVL. By exploiting the ENAH- specific conformation, we rationally designed the tightest and most selective ENAH binder to date. Our work uncovers a conformational mechanism of interaction specificity that distinguishes highly similar paralogs and establishes tools for dissecting specific Ena/VASP functions in processes including cancer cell invasion. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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