7usm

Integrin alphaM/beta2 ectodomain

spinqualitylabelsall models 7usm, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7usm is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.7Å Ligands: CA, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ITAM_HUMAN Genetic variations in ITGAM has been associated with susceptibility to systemic lupus erythematosus type 6 (SLEB6) [MIM: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 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Integrin 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA