8CRB

Cryo-EM structure of PcrV/Fab(11-E5)

8CRB の概要

• エントリーDOI: 10.2210/pdb8crb/pdb
• EMDBエントリー: 16807
• 分子名称: Heavy chain, Light chain, Maltose/maltodextrin-binding periplasmic protein,Type III secretion protein PcrV (3 entities in total)
• 機能のキーワード: antibody t3ss tip protein, antimicrobial protein
• 由来する生物種: Pseudomonas aeruginosa; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 122539.15

構造登録者

Yuan, B.,Simonis, A.,Marlovits, T.C. (登録日: 2023-03-08, 公開日: 2023-11-22)

主引用文献

Simonis, A.,Kreer, C.,Albus, A.,Rox, K.,Yuan, B.,Holzmann, D.,Wilms, J.A.,Zuber, S.,Kottege, L.,Winter, S.,Meyer, M.,Schmitt, K.,Gruell, H.,Theobald, S.J.,Hellmann, A.M.,Meyer, C.,Ercanoglu, M.S.,Cramer, N.,Munder, A.,Hallek, M.,Fatkenheuer, G.,Koch, M.,Seifert, H.,Rietschel, E.,Marlovits, T.C.,van Koningsbruggen-Rietschel, S.,Klein, F.,Rybniker, J.
Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa.
Cell, 186:5098-5113.e19, 2023

PubMed Abstract: Drug-resistant Pseudomonas aeruginosa (PA) poses an emerging threat to human health with urgent need for alternative therapeutic approaches. Here, we deciphered the B cell and antibody response to the virulence-associated type III secretion system (T3SS) in a cohort of patients chronically infected with PA. Single-cell analytics revealed a diverse B cell receptor repertoire directed against the T3SS needle-tip protein PcrV, enabling the production of monoclonal antibodies (mAbs) abrogating T3SS-mediated cytotoxicity. Mechanistic studies involving cryoelectron microscopy identified a surface-exposed C-terminal PcrV epitope as the target of highly neutralizing mAbs with broad activity against drug-resistant PA isolates. These anti-PcrV mAbs were as effective as treatment with conventional antibiotics in vivo. Our study reveals that chronically infected patients represent a source of neutralizing antibodies, which can be exploited as therapeutics against PA.

PubMed: 37918395
DOI: 10.1016/j.cell.2023.10.002

実験手法

ELECTRON MICROSCOPY (4.6 Å)