2LCZ

NMR Structure of the Complete Internal Fusion Loop from Ebolavirus GP2 at pH 7.0

2LCZ の概要

• エントリーDOI: 10.2210/pdb2lcz/pdb
• 関連するPDBエントリー: 2LCY
• NMR情報: BMRB: 17639
• 分子名称: Virion spike glycoprotein (1 entity in total)
• 機能のキーワード: viral protein
• 由来する生物種: Zaire ebolavirus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5947.69

構造登録者

Gregory, S.M.,Harada, E.,Liang, B.,Tamm, L.K. (登録日: 2011-05-12, 公開日: 2011-06-22, 最終更新日: 2024-10-30)

主引用文献

Gregory, S.M.,Harada, E.,Liang, B.,Delos, S.E.,White, J.M.,Tamm, L.K.
Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2.
Proc.Natl.Acad.Sci.USA, 108:11211-11216, 2011

PubMed Abstract: Ebolavirus (Ebov), an enveloped virus of the family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates. The viral glycoprotein (GP) is solely responsible for virus-host membrane fusion, but how it does so remains elusive. Fusion occurs after virions reach an endosomal compartment where GP is proteolytically primed by cathepsins. Fusion by primed GP is governed by an internal fusion loop found in GP2, the fusion subunit. This fusion loop contains a stretch of hydrophobic residues, some of which have been shown to be critical for GP-mediated infection. Here we present liposome fusion data and NMR structures for a complete (54-residue) disulfide-bonded internal fusion loop (Ebov FL) in a membrane mimetic. The Ebov FL induced rapid fusion of liposomes of varying compositions at pH values at or below 5.5. Consistently, circular dichroism experiments indicated that the α-helical content of the Ebov FL in the presence of either lipid-mimetic micelles or small liposomes increases in samples exposed to pH ≤5.5. NMR structures in dodecylphosphocholine micelles at pH 7.0 and 5.5 revealed a conformational change from a relatively flat extended loop structure at pH 7.0 to a structure with an ∼90° bend at pH 5.5. Induction of the bend at low pH reorients and compacts the hydrophobic patch at the tip of the FL. We propose that these changes facilitate disruption of lipids at the site of virus-host cell membrane contact and, hence, initiate Ebov fusion.

PubMed: 21690393
DOI: 10.1073/pnas.1104760108

実験手法

SOLUTION NMR