6BP2

Therapeutic human monoclonal antibody MR191 bound to a marburgvirus glycoprotein

6BP2 の概要

• エントリーDOI: 10.2210/pdb6bp2/pdb
• 分子名称: Envelope glycoprotein, Envelope glycoprotein GP2, MR191 Fab Heavy Chain, ... (7 entities in total)
• 機能のキーワード: marburg, ravn, glycoprotein, complex, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Marburg marburgvirus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 99612.73

構造登録者

King, L.B.,Fusco, M.L.,Flyak, A.I.,Ilinykh, P.A.,Huang, K.,Gunn, B.,Kirchdoerfer, R.N.,Hastie, K.M.,Sangha, A.K.,Meiler, J.,Alter, G.,Bukreyev, A.,Crowe, J.E.J.,Saphire, E.O. (登録日: 2017-11-21, 公開日: 2018-01-17, 最終更新日: 2024-11-13)

主引用文献

King, L.B.,Fusco, M.L.,Flyak, A.I.,Ilinykh, P.A.,Huang, K.,Gunn, B.,Kirchdoerfer, R.N.,Hastie, K.M.,Sangha, A.K.,Meiler, J.,Alter, G.,Bukreyev, A.,Crowe, J.E.,Saphire, E.O.
The Marburgvirus-Neutralizing Human Monoclonal Antibody MR191 Targets a Conserved Site to Block Virus Receptor Binding.
Cell Host Microbe, 23:101-109.e4, 2018

PubMed Abstract: Since their first identification 50 years ago, marburgviruses have emerged several times, with 83%-90% lethality in the largest outbreaks. Although no vaccines or therapeutics are available for human use, the human antibody MR191 provides complete protection in non-human primates when delivered several days after inoculation of a lethal marburgvirus dose. The detailed neutralization mechanism of MR191 remains outstanding. Here we present a 3.2 Å crystal structure of MR191 complexed with a trimeric marburgvirus surface glycoprotein (GP). MR191 neutralizes by occupying the conserved receptor-binding site and competing with the host receptor Niemann-Pick C1. The structure illuminates previously disordered regions of GP including the stalk, fusion loop, CXCC switch, and an N-terminal region of GP2 that wraps about the outside of GP1 to anchor a marburgvirus-specific "wing" antibody epitope. Virus escape mutations mapped far outside the MR191 receptor-binding site footprint suggest a role for these other regions in the GP quaternary structure.

PubMed: 29324225
DOI: 10.1016/j.chom.2017.12.003

実験手法

X-RAY DIFFRACTION (3.172 Å)