التفاصيل البيبلوغرافية
| العنوان: |
A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers |
| المؤلفون: |
Hwang, Theresa, Parker, Sara S, Hill, Samantha M, Ilunga, Meucci W, Grant, Robert A, Mouneimne, Ghassan, Keating, Amy E |
| المساهمون: |
Massachusetts Institute of Technology. Department of Biology |
| المصدر: |
eLife |
| بيانات النشر: |
eLife Sciences Publications, Ltd |
| سنة النشر: |
2022 |
| المجموعة: |
DSpace@MIT (Massachusetts Institute of Technology) |
| الوصف: |
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. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
eLife; https://hdl.handle.net/1721.1/146849Test; Hwang, Theresa, Parker, Sara S, Hill, Samantha M, Ilunga, Meucci W, Grant, Robert A et al. 2021. "A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers." eLife, 10. |
| الإتاحة: |
https://hdl.handle.net/1721.1/146849Test |
| حقوق: |
Creative Commons Attribution 4.0 International license ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.B1A2488B |
| قاعدة البيانات: |
BASE |
