3v4p

From Proteopedia

(Difference between revisions)

Current revision

crystal structure of a4b7 headpiece complexed with Fab ACT-1

Structural highlights

3v4p is a 8 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.15Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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/3v4p"

@@ Line 1: / Line 1: @@
-[[Image:3v4p.png|left|200px]]
-<!--
+==crystal structure of a4b7 headpiece complexed with Fab ACT-1==
-The line below this paragraph, containing "STRUCTURE_3v4p", creates the "Structure Box" on the page.
+<StructureSection load='3v4p' size='340' side='right'caption='[[3v4p]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3v4p]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V4P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V4P FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.15&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=15P:POLYETHYLENE+GLYCOL+(N=34)'>15P</scene>, <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=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></td></tr>
-{{STRUCTURE_3v4p|  PDB=3v4p  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v4p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v4p OCA], [https://pdbe.org/3v4p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v4p RCSB], [https://www.ebi.ac.uk/pdbsum/3v4p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v4p ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ITB7_HUMAN 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.
+<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.
-===crystal structure of a4b7 headpiece complexed with Fab ACT-1===
+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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3v4p" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22232704}}, adds the Publication Abstract to the page
+*[[Integrin 3D structures|Integrin 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22232704 is the PubMed ID number.
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
--->
+== References ==
-{{ABSTRACT_PUBMED_22232704}}
+<references/>
+__TOC__
-==About this Structure==
+</StructureSection>
-[[3v4p]] 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=3V4P OCA].
-==Reference==
-<ref group="xtra">PMID:022232704</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Springer, T A.]]
+[[Category: Springer TA]]
-[[Category: Yu, Y.]]
+[[Category: Yu Y]]
-[[Category: Zhu, J.]]
+[[Category: Zhu J]]
-[[Category: Cell adhesion]]
-[[Category: Madcam-1]]
-[[Category: Membrane]]

3v4p

From Proteopedia

Current revision

crystal structure of a4b7 headpiece complexed with Fab ACT-1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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