View source for 7lxf


==ENAH EVH1 domain bound to peptide from protein PCARE==
<StructureSection load='7lxf' size='340' side='right'caption='[[7lxf]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lxf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LXF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LXF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7lxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lxf OCA], [https://pdbe.org/7lxf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lxf RCSB], [https://www.ebi.ac.uk/pdbsum/7lxf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lxf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PCARE_HUMAN PCARE_HUMAN] Retinitis pigmentosa. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/PCARE_HUMAN PCARE_HUMAN] Plays an essential role for normal photoreceptor cell maintenance and vision.<ref>PMID:20398886</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers.,Hwang T, Parker SS, Hill SM, Ilunga MW, Grant RA, Mouneimne G, Keating AE Elife. 2021 Dec 2;10. pii: 70601. doi: 10.7554/eLife.70601. PMID:34854809<ref>PMID:34854809</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lxf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Grant RA]]
[[Category: Hwang T]]
[[Category: Keating AE]]