7lxf: Difference between revisions

Latest revision as of 16:00, 18 October 2023

ENAH EVH1 domain bound to peptide from protein PCARE

Structural highlights

7lxf is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.65Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PCARE_HUMAN Retinitis pigmentosa. The disease is caused by variants affecting the gene represented in this entry.

Function

PCARE_HUMAN Plays an essential role for normal photoreceptor cell maintenance and vision.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nishimura DY, Baye LM, Perveen R, Searby CC, Avila-Fernandez A, Pereiro I, Ayuso C, Valverde D, Bishop PN, Manson FD, Urquhart J, Stone EM, Slusarski DC, Black GC, Sheffield VC. Discovery and functional analysis of a retinitis pigmentosa gene, C2ORF71. Am J Hum Genet. 2010 May 14;86(5):686-95. PMID:20398886 doi:10.1016/j.ajhg.2010.03.005
↑ Hwang T, Parker SS, Hill SM, Ilunga MW, Grant RA, Mouneimne G, Keating AE. A distributed residue network permits conformational binding specificity in a conserved family of actin remodelers. Elife. 2021 Dec 2;10. pii: 70601. doi: 10.7554/eLife.70601. PMID:34854809 doi:https://dx.doi.org/10.7554/eLife.70601

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OCA

[1] Nishimura DY, Baye LM, Perveen R, Searby CC, Avila-Fernandez A, Pereiro I, Ayuso C, Valverde D, Bishop PN, Manson FD, Urquhart J, Stone EM, Slusarski DC, Black GC, Sheffield VC. Discovery and functional analysis of a retinitis pigmentosa gene, C2ORF71. Am J Hum Genet. 2010 May 14;86(5):686-95. PMID:20398886 doi:10.1016/j.ajhg.2010.03.005

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

[1]

[2]

@@ Line 3: / Line 3: @@
 <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. 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 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='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>
+</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 ==
@@ Line 19: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Grant, R A]]
+[[Category: Grant RA]]
-[[Category: Hwang, T]]
+[[Category: Hwang T]]
-[[Category: Keating, A E]]
+[[Category: Keating AE]]
-[[Category: Complex]]
-[[Category: Cytoskeleton]]
-[[Category: Protein binding]]

7lxf: Difference between revisions

Latest revision as of 16:00, 18 October 2023

ENAH EVH1 domain bound to peptide from protein PCARE

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

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