7lxf: Difference between revisions

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==ENAH EVH1 domain bound to peptide from protein PCARE==

== Structural highlights ==

<table><tr><td colspan='2'>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>

<table><tr><td colspan='2'>[[7lxf]] is a 1 chain structure. 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='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>

== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Large Structures]]

[[Category: Grant RA]]

[[Category: Grant, R A]]

[[Category: Hwang T]]

[[Category: Hwang, T]]

[[Category: Keating AE]]

[[Category: Keating, A E]]

[[Category: Complex]]

[[Category: Cytoskeleton]]

[[Category: Protein binding]]

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 ==ENAH EVH1 domain bound to peptide from protein PCARE==
-<StructureSection load='7lxf' size='340' side='right'caption='[[7lxf]]' scene=''>
+<StructureSection load='7lxf' size='340' side='right'caption='[[7lxf]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>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>
+<table><tr><td colspan='2'>[[7lxf]] is a 1 chain structure. 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='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>
+<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: Large Structures]]
-[[Category: Grant RA]]
+[[Category: Grant, R A]]
-[[Category: Hwang T]]
+[[Category: Hwang, T]]
-[[Category: Keating AE]]
+[[Category: Keating, A E]]
+[[Category: Complex]]
+[[Category: Cytoskeleton]]
+[[Category: Protein binding]]