3v4v: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| 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]] 3.10Å' 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> | |||
</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='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> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:22232704</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Integrin|Integrin]] | *[[Integrin|Integrin]] | ||
*[[Monoclonal Antibody|Monoclonal Antibody]] | |||
== | == References == | ||
< | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Springer, T A | [[Category: Springer, T A]] | ||
[[Category: Yu, Y | [[Category: Yu, Y]] | ||
[[Category: Zhu, J | [[Category: Zhu, J]] | ||
[[Category: Cell adhesion]] | [[Category: Cell adhesion]] | ||
[[Category: Madcam-1]] | [[Category: Madcam-1]] | ||
[[Category: Membrane]] | [[Category: Membrane]] | ||
Revision as of 20:45, 9 December 2014
crystal structure of a4b7 headpiece complexed with Fab ACT-1 and RO0505376crystal structure of a4b7 headpiece complexed with Fab ACT-1 and RO0505376
Structural highlights
Publication Abstract from PubMedThe 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. See AlsoReferences
|
| ||||||||||||||||||||