7USL

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

Summary for 7USL

• Entry DOI: 10.2210/pdb7usl/pdb
• EMDB information: 26738
• Descriptor: Integrin alpha-M, Integrin beta, Bifunctional hemolysin-adenylate cyclase, ... (9 entities in total)
• Functional Keywords: receptor, complex, integrin, toxin
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 362304.30

Authors

Goldsmith, J.A.,McLellan, J.S. (deposition date: 2022-04-25, release date: 2022-08-17, Last modification date: 2024-11-13)

Primary citation

Goldsmith, J.A.,DiVenere, A.M.,Maynard, J.A.,McLellan, J.S.
Structural basis for non-canonical integrin engagement by Bordetella adenylate cyclase toxin.
Cell Rep, 40:111196-111196, 2022

PubMed Abstract: Integrins are ubiquitous cell-surface heterodimers that are exploited by pathogens and toxins, including leukotoxins that target β integrins on phagocytes. The Bordetella adenylate cyclase toxin (ACT) uses the αβ 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 Å resolution structure of an ACT fragment bound to αβ. This structure reveals that ACT interacts with the headpiece and calf-2 of the α subunit in a non-canonical manner specific to bent, inactive αβ. Neutralizing antibody epitopes map to ACT residues involved in α binding, providing the basis for antibody-mediated attachment inhibition. Furthermore, binding to αβ 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.

PubMed: 35977491
DOI: 10.1016/j.celrep.2022.111196

Experimental method

ELECTRON MICROSCOPY (2.7 Å)