3qa3
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal Structure of A-domain in complex with antibody== | |
| - | + | <StructureSection load='3qa3' size='340' side='right' caption='[[3qa3]], [[Resolution|resolution]] 3.00Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3qa3]] is a 12 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=3QA3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QA3 FirstGlance]. <br> | |
| - | ==Disease== | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3q3g|3q3g]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ITGAM, CD11B, CR3A ([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=3qa3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qa3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qa3 RCSB], [http://www.ebi.ac.uk/pdbsum/3qa3 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[http://www.uniprot.org/uniprot/ITAM_HUMAN ITAM_HUMAN]] Genetic variations in ITGAM has been associated with susceptibility to systemic lupus erythematosus type 6 (SLEB6) [MIM:[http://omim.org/entry/609939 609939]]. Systemic lupus erythematosus (SLE) is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. | [[http://www.uniprot.org/uniprot/ITAM_HUMAN ITAM_HUMAN]] Genetic variations in ITGAM has been associated with susceptibility to systemic lupus erythematosus type 6 (SLEB6) [MIM:[http://omim.org/entry/609939 609939]]. Systemic lupus erythematosus (SLE) is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. | ||
| - | + | == Function == | |
| - | ==Function== | + | |
[[http://www.uniprot.org/uniprot/ITAM_HUMAN ITAM_HUMAN]] Integrin alpha-M/beta-2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles. It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin alpha-M/beta-2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain. | [[http://www.uniprot.org/uniprot/ITAM_HUMAN ITAM_HUMAN]] Integrin alpha-M/beta-2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles. It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin alpha-M/beta-2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A central feature of integrin interaction with physiologic ligands is the monodentate binding of a ligand carboxylate to a Mg(2+) ion hexacoordinated at the metal ion-dependent adhesion site (MIDAS) in the integrin A domain. This interaction stabilizes the A domain in the high-affinity state, which is distinguished from the default low-affinity state by tertiary changes in the domain that culminate in cell adhesion. Small molecule ligand-mimetic integrin antagonists act as partial agonists, eliciting similar activating conformational changes in the A domain, which has contributed to paradoxical adhesion and increased patient mortality in large clinical trials. As with other ligand-mimetic integrin antagonists, the function-blocking mAb 107 binds MIDAS of integrin CD11b/CD18 A domain (CD11bA), but in contrast, it favors the inhibitory Ca(2+) ion over the Mg(2+) ion at MIDAS. We determined the crystal structures of the Fab fragment of mAb 107 complexed to the low- and high-affinity states of CD11bA. Favored binding of the Ca(2+) ion at MIDAS is caused by the unusual symmetric bidentate ligation of a Fab-derived ligand Asp to a heptacoordinated MIDAS Ca(2+) ion. Binding of the Fab fragment of mAb 107 to CD11bA did not trigger the activating tertiary changes in the domain or in the full-length integrin. These data show that the denticity of the ligand Asp/Glu can modify the divalent cation selectivity at MIDAS and hence integrin function. Stabilizing the Ca(2+) ion at MIDAS by bidentate ligation to a ligand Asp/Glu may provide one approach for designing pure integrin antagonists. | ||
| - | + | Stable Coordination of the Inhibitory Ca2+ Ion at the Metal Ion-Dependent Adhesion Site in Integrin CD11b/CD18 by an Antibody-Derived Ligand Aspartate: Implications for Integrin Regulation and Structure-Based Drug Design.,Mahalingam B, Ajroud K, Alonso JL, Anand S, Adair BD, Horenstein AL, Malavasi F, Xiong JP, Arnaout MA J Immunol. 2011 Nov 16. PMID:22095715<ref>PMID:22095715</ref> | |
| - | + | ||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
==See Also== | ==See Also== | ||
*[[Antibody|Antibody]] | *[[Antibody|Antibody]] | ||
| - | + | *[[Integrin|Integrin]] | |
| - | == | + | == References == |
| - | + | <references/> | |
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
| - | [[Category: Arnaout, M A | + | [[Category: Arnaout, M A]] |
| - | [[Category: Mahalingam, B | + | [[Category: Mahalingam, B]] |
| - | [[Category: Xiong, J P | + | [[Category: Xiong, J P]] |
[[Category: Immune system- cell adhesion complex]] | [[Category: Immune system- cell adhesion complex]] | ||
Revision as of 10:41, 19 December 2014
Crystal Structure of A-domain in complex with antibody
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