7LXF
ENAH EVH1 domain bound to peptide from protein PCARE
Summary for 7LXF
| Entry DOI | 10.2210/pdb7lxf/pdb |
| Descriptor | Protein enabled homolog,Photoreceptor cilium actin regulator (2 entities in total) |
| Functional Keywords | complex, cytoskeleton, protein binding |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 17091.22 |
| Authors | Hwang, T.,Grant, R.A.,Keating, A.E. (deposition date: 2021-03-03, release date: 2021-11-24, Last modification date: 2023-10-18) |
| Primary citation | Hwang, T.,Parker, S.S.,Hill, S.M.,Ilunga, M.W.,Grant, R.A.,Mouneimne, G.,Keating, A.E. A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers. Elife, 10:-, 2021 Cited by PubMed Abstract: 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. PubMed: 34854809DOI: 10.7554/eLife.70601 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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