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3v4v

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Revision as of 23:21, 5 August 2016

crystal structure of a4b7 headpiece complexed with Fab ACT-1 and RO0505376

Structural highlights

3v4v is a 8 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
Related:	3v4p
Gene:	ITGA4, CD49D (HUMAN), ITGB7 (HUMAN)
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. [ITB7_HUMAN] Integrin alpha-4/beta-7 (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT). Integrin alpha-4/beta-7 interacts with the cell surface adhesion molecules MADCAM1 which is normally expressed by the vascular endothelium of the gastrointestinal tract. Interacts also with VCAM1 and fibronectin, an extracellular matrix component. It recognizes one or more domains within the alternatively spliced CS-1 region of fibronectin. Interactions involves the tripeptide L-D-T in MADCAM1, and L-D-V in fibronectin. Binds to HIV-1 gp120, thereby allowing the virus to enter GALT, which is thought to be the major trigger of AIDS disease. Interaction would involve a tripeptide L-D-I in HIV-1 gp120. Integrin alpha-E/beta-7 (HML-1) is a receptor for E-cadherin.

Publication Abstract from PubMed

The lymphocyte homing receptor integrin alpha(4)beta(7) is unusual for its ability to mediate both rolling and firm adhesion. alpha(4)beta(1) and alpha(4)beta(7) are targeted by therapeutics approved for multiple sclerosis and Crohn's disease. Here, we show by electron microscopy and crystallography how two therapeutic Fabs, a small molecule (RO0505376), and mucosal adhesion molecule-1 (MAdCAM-1) bind alpha(4)beta(7). A long binding groove at the alpha(4)-beta(7) interface for immunoglobulin superfamily domains differs in shape from integrin pockets that bind Arg-Gly-Asp motifs. RO0505376 mimics an Ile/Leu-Asp motif in alpha(4) ligands, and orients differently from Arg-Gly-Asp mimics. A novel auxiliary residue at the metal ion-dependent adhesion site in alpha(4)beta(7) is essential for binding to MAdCAM-1 in Mg(2+) yet swings away when RO0505376 binds. A novel intermediate conformation of the alpha(4)beta(7) headpiece binds MAdCAM-1 and supports rolling adhesion. Lack of induction of the open headpiece conformation by ligand binding enables rolling adhesion to persist until integrin activation is signaled.

Structural specializations of alpha(4)beta(7), an integrin that mediates rolling adhesion.,Yu Y, Zhu J, Mi LZ, Walz T, Sun H, Chen J, Springer TA J Cell Biol. 2012 Jan 9;196(1):131-46. PMID:22232704^[1]

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

References

↑ Yu Y, Zhu J, Mi LZ, Walz T, Sun H, Chen J, Springer TA. Structural specializations of alpha(4)beta(7), an integrin that mediates rolling adhesion. J Cell Biol. 2012 Jan 9;196(1):131-46. PMID:22232704 doi:10.1083/jcb.201110023

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3v4v"

@@ Line 1: / Line 1: @@
 ==crystal structure of a4b7 headpiece complexed with Fab ACT-1 and RO0505376==
 <StructureSection load='3v4v' size='340' side='right' caption='[[3v4v]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3v4v]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V4V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V4V FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3v4v]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V4V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3V4V FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0DU:N-(2,6-DICHLOROBENZOYL)-4-[1,6-DIMETHYL-2-OXO-4-(TRIFLUOROMETHYL)-1,2-DIHYDROPYRIDIN-3-YL]-L-PHENYLALANINE'>0DU</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3v4p|3v4p]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ITGA4, CD49D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), ITGB7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ITGA4, CD49D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ITGB7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3v4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v4v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3v4v RCSB], [http://www.ebi.ac.uk/pdbsum/3v4v PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3v4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v4v OCA], [http://pdbe.org/3v4v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3v4v RCSB], [http://www.ebi.ac.uk/pdbsum/3v4v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3v4v ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3v4v" style="background-color:#fffaf0;"></div>
 ==See Also==
 *[[Integrin|Integrin]]
-*[[Monoclonal Antibody|Monoclonal Antibody]]
+*[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
-[[Category: Mus musculus]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Springer, T A]]
 [[Category: Yu, Y]]

3v4v

From Proteopedia

Revision as of 23:21, 5 August 2016

crystal structure of a4b7 headpiece complexed with Fab ACT-1 and RO0505376

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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