7LSG

Crystal structure of the human neutralizing antibody Fab fragment T025 bound to TBEV EDIII (Siberian Subtype)

7LSG の概要

• エントリーDOI: 10.2210/pdb7lsg/pdb
• 分子名称: T025 Fab Heavy Chain, T025 Fab Light Chain, Core protein, ... (4 entities in total)
• 機能のキーワード: tick-borne encephalitis virus, antibody, ediii, tbev, immune system, immune system-viral protein complex, immune system/viral protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 58937.87

構造登録者

Keeffe, J.R.,Bjorkman, P.J. (登録日: 2021-02-18, 公開日: 2021-04-07, 最終更新日: 2024-10-23)

主引用文献

Agudelo, M.,Palus, M.,Keeffe, J.R.,Bianchini, F.,Svoboda, P.,Salat, J.,Peace, A.,Gazumyan, A.,Cipolla, M.,Kapoor, T.,Guidetti, F.,Yao, K.H.,Elsterova, J.,Teislerova, D.,Chrdle, A.,Honig, V.,Oliveira, T.,West, A.P.,Lee, Y.E.,Rice, C.M.,MacDonald, M.R.,Bjorkman, P.J.,Ruzek, D.,Robbiani, D.F.,Nussenzweig, M.C.
Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease.
J.Exp.Med., 218:-, 2021

PubMed Abstract: Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI-EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.

PubMed: 33831141
DOI: 10.1084/jem.20210236

実験手法

X-RAY DIFFRACTION (1.86 Å)