- EMDB-16805: Cryo-EM structure of PcrV/Fab(30-B8) -
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基本情報
登録情報
データベース: EMDB / ID: EMD-16805
タイトル
Cryo-EM structure of PcrV/Fab(30-B8)
マップデータ
試料
複合体: PcrV-Fab(30-B8)
タンパク質・ペプチド: Heavy chain
タンパク質・ペプチド: light chain
タンパク質・ペプチド: Maltose/maltodextrin-binding periplasmic protein,Type III secretion protein PcrV
キーワード
antibody T3SS Tip protein / ANTIMICROBIAL PROTEIN
機能・相同性
機能・相同性情報
type III protein secretion system complex / protein secretion by the type III secretion system / detection of maltose stimulus / maltose transport complex / carbohydrate transport / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing ...type III protein secretion system complex / protein secretion by the type III secretion system / detection of maltose stimulus / maltose transport complex / carbohydrate transport / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / ATP-binding cassette (ABC) transporter complex / cell chemotaxis / outer membrane-bounded periplasmic space / periplasmic space / DNA damage response / extracellular space / membrane 類似検索 - 分子機能
Low calcium response V antigen / Virulence-associated V antigen superfamily / V antigen (LcrV) protein / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein 類似検索 - ドメイン・相同性
Type III secretion protein PcrV / Maltose/maltodextrin-binding periplasmic protein 類似検索 - 構成要素
ジャーナル: Cell / 年: 2023 タイトル: Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa. 著者: Alexander Simonis / Christoph Kreer / Alexandra Albus / Katharina Rox / Biao Yuan / Dmitriy Holzmann / Joana A Wilms / Sylvia Zuber / Lisa Kottege / Sandra Winter / Meike Meyer / Kristin ...著者: Alexander Simonis / Christoph Kreer / Alexandra Albus / Katharina Rox / Biao Yuan / Dmitriy Holzmann / Joana A Wilms / Sylvia Zuber / Lisa Kottege / Sandra Winter / Meike Meyer / Kristin Schmitt / Henning Gruell / Sebastian J Theobald / Anna-Maria Hellmann / Christina Meyer / Meryem Seda Ercanoglu / Nina Cramer / Antje Munder / Michael Hallek / Gerd Fätkenheuer / Manuel Koch / Harald Seifert / Ernst Rietschel / Thomas C Marlovits / Silke van Koningsbruggen-Rietschel / Florian Klein / Jan Rybniker / 要旨: 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 ...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.