View source for 7usm


==Integrin alphaM/beta2 ectodomain==
<StructureSection load='7usm' size='340' side='right'caption='[[7usm]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7usm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7USM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7USM FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7usm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7usm OCA], [https://pdbe.org/7usm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7usm RCSB], [https://www.ebi.ac.uk/pdbsum/7usm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7usm ProSAT]</span></td></tr>
</table>
== Disease ==
[https://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:[https://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 ==
[https://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.
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== Publication Abstract from PubMed ==
Integrins are ubiquitous cell-surface heterodimers that are exploited by pathogens and toxins, including leukotoxins that target beta(2) integrins on phagocytes. The Bordetella adenylate cyclase toxin (ACT) uses the alpha(M)beta(2) integrin as a receptor, but the structural basis for integrin binding and neutralization by antibodies is poorly understood. Here, we use cryoelectron microscopy to determine a 2.7 A resolution structure of an ACT fragment bound to alpha(M)beta(2). This structure reveals that ACT interacts with the headpiece and calf-2 of the alpha(M) subunit in a non-canonical manner specific to bent, inactive alpha(M)beta(2). Neutralizing antibody epitopes map to ACT residues involved in alpha(M) binding, providing the basis for antibody-mediated attachment inhibition. Furthermore, binding to alpha(M)beta(2) positions the essential ACT acylation sites, which are conserved among toxins exported by type I secretion systems, at the cell membrane. These findings reveal a structural mechanism for integrin-mediated attachment and explain antibody-mediated neutralization of ACT intoxication.

Structural basis for non-canonical integrin engagement by Bordetella adenylate cyclase toxin.,Goldsmith JA, DiVenere AM, Maynard JA, McLellan JS Cell Rep. 2022 Aug 16;40(7):111196. doi: 10.1016/j.celrep.2022.111196. PMID:35977491<ref>PMID:35977491</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7usm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Integrin 3D structures|Integrin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Goldsmith JA]]
[[Category: McLellan JS]]