7AKV

The cryo-EM structure of the Vag8-C1 inhibitor complex

7AKV の概要

• エントリーDOI: 10.2210/pdb7akv/pdb
• EMDBエントリー: 11814
• 分子名称: Plasma protease C1 inhibitor, Vag8 (2 entities in total)
• 機能のキーワード: complex bacterial protein human protein immune system inhibitor, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 136273.81

構造登録者

Johnson, S.,Lea, S.M.,Deme, J.C.,Furlong, E.,Dhillon, A. (登録日: 2020-10-02, 公開日: 2021-06-16, 最終更新日: 2024-10-23)

主引用文献

Dhillon, A.,Deme, J.C.,Furlong, E.,Roem, D.,Jongerius, I.,Johnson, S.,Lea, S.M.
Molecular Basis for Bordetella pertussis Interference with Complement, Coagulation, Fibrinolytic, and Contact Activation Systems: the Cryo-EM Structure of the Vag8-C1 Inhibitor Complex.
Mbio, 12:-, 2021

PubMed Abstract: Complement, contact activation, coagulation, and fibrinolysis are serum protein cascades that need strict regulation to maintain human health. Serum glycoprotein, a C1 inhibitor (C1-INH), is a key regulator (inhibitor) of serine proteases of all the above-mentioned pathways. Recently, an autotransporter protein, virulence-associated gene 8 (Vag8), produced by the whooping cough pathogen, , was shown to bind to C1-INH and interfere with its function. Here, we present the structure of the Vag8-C1-INH complex determined using cryo-electron microscopy at a 3.6-Å resolution. The structure shows a unique mechanism of C1-INH inhibition not employed by other pathogens, where Vag8 sequesters the reactive center loop of C1-INH, preventing its interaction with the target proteases. The structure of a 10-kDa protein complex is one of the smallest to be determined using cryo-electron microscopy at high resolution. The structure reveals that C1-INH is sequestered in an inactivated state by burial of the reactive center loop in Vag8. By so doing, the bacterium is able to simultaneously perturb the many pathways regulated by C1-INH. Virulence mechanisms such as the one described here assume more importance given the emerging evidence about dysregulation of contact activation, coagulation, and fibrinolysis leading to COVID-19 pneumonia.

PubMed: 33758081
DOI: 10.1128/mBio.02823-20

実験手法

ELECTRON MICROSCOPY (3.6 Å)