This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
3qa3
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | + | ==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
| |||||||||||
