9JBQ

Structure of the complex between h1F3 Fab and PcrV fragment

Summary for 9JBQ

• Entry DOI: 10.2210/pdb9jbq/pdb
• Descriptor: Heavy chain, light chain, PcrV, ... (4 entities in total)
• Functional Keywords: complex, fab, antimicrobial protein, antimicrobial protein-immune system complex, antimicrobial protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 62646.86

Authors

Numata, S.,Hara, T.,Izawa, M.,Okuno, Y.,Sato, Y.,Yamane, S.,Maki, H.,Sato, T.,Yamano, Y. (deposition date: 2024-08-27, release date: 2024-09-11, Last modification date: 2024-10-16)

Primary citation

Numata, S.,Hara, T.,Izawa, M.,Okuno, Y.,Sato, Y.,Yamane, S.,Maki, H.,Sato, T.,Yamano, Y.
Novel humanized anti-PcrV monoclonal antibody COT-143 protects mice from lethal Pseudomonas aeruginosa infection via inhibition of toxin translocation by the type III secretion system.
Antimicrob.Agents Chemother., 68:e0069424-e0069424, 2024

PubMed Abstract: Treatment of infection is challenging due to its intrinsic and acquired antibiotic resistance. As the number of current therapeutic options for infections is limited, developing novel treatments against the pathogen is an urgent clinical priority. The suppression of virulence of could be a new therapeutic option, and the type III secretion system (T3SS), which enables the bacteria to translocate various kinds of toxins into host cells and inhibits cellular functions, is considered as one possible target. In this report, we examined T3SS inhibition by COT-143/INFEX702, a humanized monoclonal antibody against PcrV, T3SS component, and present the crystal structure of the antibody-PcrV complex. COT-143 inhibited T3SS-dependent cytotoxicity and protected mice from the mortality caused by infection. The inhibition of cytotoxicity coincided with inhibition of translocon formation in a host cell membrane, which is necessary for T3SS intoxication. COT-143 protected murine neutrophils and facilitated phagocytosis of . These results suggest that COT-143 facilitates clearance by protecting neutrophil via inhibition of T3SS-dependent toxin translocation. This is the first report to show that an anti-PcrV antibody directly interferes with translocon formation to inhibit intoxication of host cells.

PubMed: 39269189
DOI: 10.1128/aac.00694-24

Experimental method

X-RAY DIFFRACTION (2 Å)