6WLA

Antigen binding fragment of ch128.1

これはPDB形式変換不可エントリーです。

6WLA の概要

• エントリーDOI: 10.2210/pdb6wla/pdb
• 分子名称: Fab ch128.1 heavy chain, Fab ch128.1 light chain, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: antibody, anti-hutfr1, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 141144.87

構造登録者

Helguera, G.,Rodriguez, J.A.,Sawaya, M.,Cascio, D.,Zink, S.,Ziegenbein, J.,Short, C. (登録日: 2020-04-18, 公開日: 2021-03-24, 最終更新日: 2024-10-16)

主引用文献

Hickerson, B.T.,Daniels-Wells, T.R.,Payes, C.,Clark, L.E.,Candelaria, P.V.,Bailey, K.W.,Sefing, E.J.,Zink, S.,Ziegenbein, J.,Abraham, J.,Helguera, G.,Penichet, M.L.,Gowen, B.B.
Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections.
Nat Commun, 13:558-558, 2022

PubMed Abstract: Five New World mammarenaviruses (NWMs) cause life-threatening hemorrhagic fever (HF). Cellular entry by these viruses is mediated by human transferrin receptor 1 (hTfR1). Here, we demonstrate that an antibody (ch128.1/IgG1) which binds the apical domain of hTfR1, potently inhibits infection of attenuated and pathogenic NWMs in vitro. Computational docking of the antibody Fab crystal structure onto the known structure of hTfR1 shows an overlapping receptor-binding region shared by the Fab and the viral envelope glycoprotein GP1 subunit that binds hTfR1, and we demonstrate competitive inhibition of NWM GP1 binding by ch128.1/IgG1 as the principal mechanism of action. Importantly, ch128.1/IgG1 protects hTfR1-expressing transgenic mice against lethal NWM challenge. Additionally, the antibody is well-tolerated and only partially reduces ferritin uptake. Our findings provide the basis for the development of a novel, host receptor-targeted antibody therapeutic broadly applicable to the treatment of HF of NWM etiology.

PubMed: 35091550
DOI: 10.1038/s41467-021-27949-3

実験手法

X-RAY DIFFRACTION (2.6 Å)