3CSY

Crystal structure of the trimeric prefusion Ebola virus glycoprotein in complex with a neutralizing antibody from a human survivor

3CSY の概要

• エントリーDOI: 10.2210/pdb3csy/pdb
• 分子名称: Fab KZ52 heavy chain, Fab KZ52 light chain, Envelope glycoprotein GP1, ... (8 entities in total)
• 機能のキーワード: glycoprotein-antibody complex, immune system-viral protein complex, immune system/viral protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: GP2: Virion membrane; Single-pass type I membrane protein. GP1: Virion membrane; Peripheral membrane protein. GP2-delta: Secreted: Q05320; GP2: Virion membrane; Single-pass type I membrane protein (By similarity). GP1: Virion membrane; Peripheral membrane protein (By similarity). GP2-delta: Secreted (By similarity): P87666
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 406070.53

構造登録者

Lee, J.E.,Fusco, M.L.,Hessell, A.J.,Oswald, W.B.,Burton, D.R.,Saphire, E.O. (登録日: 2008-04-10, 公開日: 2008-07-08, 最終更新日: 2024-10-30)

主引用文献

Lee, J.E.,Fusco, M.L.,Hessell, A.J.,Oswald, W.B.,Burton, D.R.,Saphire, E.O.
Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor.
Nature, 454:177-182, 2008

PubMed Abstract: Ebola virus (EBOV) entry requires the surface glycoprotein (GP) to initiate attachment and fusion of viral and host membranes. Here we report the crystal structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to the conserved receptor-binding site sequestered in the chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion and may explain why survivors have insignificant neutralizing antibody titres. KZ52 recognizes a protein epitope at the chalice base where it clamps several regions of the pre-fusion GP2 to the amino terminus of GP1. This structure provides a template for unravelling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development.

PubMed: 18615077
DOI: 10.1038/nature07082

実験手法

X-RAY DIFFRACTION (3.4 Å)