5HJ3

Crystal structure of host-primed Ebola virus GP, GPcl.

5HJ3 の概要

• エントリーDOI: 10.2210/pdb5hj3/pdb
• 分子名称: Envelope glycoprotein, KZ52 Antibody Fragment, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: ebola virus, eov, ebolavirus, gp, glycoprotein, gpcl, cleaved, primed, proteolytically, receptor binding pocket, crest, trough, mr72, kz52, broadly neutralizing, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Ebola virus sp.; 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 P87666
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 336368.72

構造登録者

Bornholdt, Z.A.,Fusco, M.L.,Saphire, E.O. (登録日: 2016-01-12, 公開日: 2016-03-09, 最終更新日: 2024-10-30)

主引用文献

Bornholdt, Z.A.,Ndungo, E.,Fusco, M.L.,Bale, S.,Flyak, A.I.,Crowe, J.E.,Chandran, K.,Saphire, E.O.
Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies.
Mbio, 7:e02154-e02115, 2016

PubMed Abstract: The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.

PubMed: 26908579
DOI: 10.1128/mBio.02154-15

実験手法

X-RAY DIFFRACTION (3.3 Å)