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.

7usl

From Proteopedia

Jump to: navigation, search

Integrin alphaM/beta2 ectodomain in complex with adenylate cyclase toxin RTX751 and M1F5 Fab

Structural highlights

7usl is a 5 chain structure with sequence from Bordetella pertussis and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
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 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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

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