9p95

From Proteopedia

(Difference between revisions)

Current revision

CryoEM structure of integrin alpha4beta7 bound to MAdCAM-1

Structural highlights

9p95 is a 3 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:	Electron Microscopy, Resolution 3.05Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ITA4_HUMAN Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells.

Publication Abstract from PubMed

Integrins bind ligands between their alpha (alpha) and beta (beta) subunits and transmit signals through conformational changes. Early in chordate evolution, some alpha subunits acquired an "inserted" (I) domain that expanded integrin's ligand-binding repertoire but obstructed the ancestral ligand pocket, seemingly blocking conventional integrin activation. Here, we compare cryo-electron microscopy structures of apo and ligand-bound states of the I domain-containing alphaEbeta(7) integrin and the I domain-lacking alpha(4)beta(7) integrin to illuminate how the I domain intrinsically mimics an extrinsic ligand to preserve integrin function. We trace the I domain's evolutionary origin to an ancestral collagen-collagen interaction domain, identifying an ancient molecular exaptation that facilitated integrin activation immediately upon I domain insertion. Our analyses reveal the evolutionary and biochemical basis of expanded cellular communication in vertebrates.

Molecular exaptation by the integrin alphaI domain.,Hollis JA, Chan MC, Malik HS, Campbell MG Sci Adv. 2025 Sep 12;11(37):eadx9567. doi: 10.1126/sciadv.adx9567. Epub 2025 Sep , 10. PMID:40929264^[1]

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

References

↑ Hollis JA, Chan MC, Malik HS, Campbell MG. Molecular exaptation by the integrin αI domain. Sci Adv. 2025 Sep 12;11(37):eadx9567. PMID:40929264 doi:10.1126/sciadv.adx9567

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9p95"

Categories: Homo sapiens | Large Structures | Campbell MG | Hollis JA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9p95 is ON HOLD
+==CryoEM structure of integrin alpha4beta7 bound to MAdCAM-1==
+<StructureSection load='9p95' size='340' side='right'caption='[[9p95]], [[Resolution|resolution]] 3.05&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9p95]] is a 3 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=9P95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9P95 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.05&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=9p95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9p95 OCA], [https://pdbe.org/9p95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9p95 RCSB], [https://www.ebi.ac.uk/pdbsum/9p95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9p95 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ITA4_HUMAN ITA4_HUMAN] Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Integrins bind ligands between their alpha (alpha) and beta (beta) subunits and transmit signals through conformational changes. Early in chordate evolution, some alpha subunits acquired an "inserted" (I) domain that expanded integrin's ligand-binding repertoire but obstructed the ancestral ligand pocket, seemingly blocking conventional integrin activation. Here, we compare cryo-electron microscopy structures of apo and ligand-bound states of the I domain-containing alphaEbeta(7) integrin and the I domain-lacking alpha(4)beta(7) integrin to illuminate how the I domain intrinsically mimics an extrinsic ligand to preserve integrin function. We trace the I domain's evolutionary origin to an ancestral collagen-collagen interaction domain, identifying an ancient molecular exaptation that facilitated integrin activation immediately upon I domain insertion. Our analyses reveal the evolutionary and biochemical basis of expanded cellular communication in vertebrates.
-Authors: Hollis, J.A., Campbell, M.G.
+Molecular exaptation by the integrin alphaI domain.,Hollis JA, Chan MC, Malik HS, Campbell MG Sci Adv. 2025 Sep 12;11(37):eadx9567. doi: 10.1126/sciadv.adx9567. Epub 2025 Sep , 10. PMID:40929264<ref>PMID:40929264</ref>
-Description: CryoEM structure of integrin alpha4beta7 bound to MAdCAM-1
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Campbell, M.G]]
+<div class="pdbe-citations 9p95" style="background-color:#fffaf0;"></div>
-[[Category: Hollis, J.A]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Campbell MG]]
+[[Category: Hollis JA]]

9p95

From Proteopedia

Current revision

CryoEM structure of integrin alpha4beta7 bound to MAdCAM-1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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