7usl
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Integrin alphaM/beta2 ectodomain in complex with adenylate cyclase toxin RTX751 and M1F5 Fab== |
| - | <StructureSection load='7usl' size='340' side='right'caption='[[7usl]]' scene=''> | + | <StructureSection load='7usl' size='340' side='right'caption='[[7usl]], [[Resolution|resolution]] 2.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7usl]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bordetella_pertussis Bordetella pertussis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7USL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7USL FirstGlance]. <br> |
| - | </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=7usl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7usl OCA], [https://pdbe.org/7usl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7usl RCSB], [https://www.ebi.ac.uk/pdbsum/7usl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7usl ProSAT]</span></td></tr> | + | </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=FUC:ALPHA-L-FUCOSE'>FUC</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=7usl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7usl OCA], [https://pdbe.org/7usl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7usl RCSB], [https://www.ebi.ac.uk/pdbsum/7usl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7usl ProSAT]</span></td></tr> | ||
</table> | </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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Integrins are ubiquitous cell-surface heterodimers that are exploited by pathogens and toxins, including leukotoxins that target beta2 integrins on phagocytes. The Bordetella adenylate cyclase toxin (ACT) uses the alphaMbeta2 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 alphaMbeta2. This structure reveals that ACT interacts with the headpiece and calf-2 of the alphaM subunit in a non-canonical manner specific to bent, inactive alphaMbeta2. Neutralizing antibody epitopes map to ACT residues involved in alphaM binding, providing the basis for antibody-mediated attachment inhibition. Furthermore, binding to alphaMbeta2 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7usl" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bordetella pertussis]] | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Goldsmith JA]] |
| + | [[Category: McLellan JS]] | ||
Current revision
Integrin alphaM/beta2 ectodomain in complex with adenylate cyclase toxin RTX751 and M1F5 Fab
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