6NTX

Respiratory syncytial virus fusion protein N-terminal heptad repeat domain+VIQKI

6NTX の概要

• エントリーDOI: 10.2210/pdb6ntx/pdb
• 分子名称: Fusion glycoprotein F0 (3 entities in total)
• 機能のキーワード: fusion protein, fusion inhibitor, six-helix bundle, antiviral protein
• 由来する生物種: Human respiratory syncytial virus A; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 19518.87

構造登録者

Outlaw, V.K.,Kreitler, D.F.,Gellman, S.H. (登録日: 2019-01-30, 公開日: 2019-07-17, 最終更新日: 2024-10-23)

主引用文献

Outlaw, V.K.,Bottom-Tanzer, S.,Kreitler, D.F.,Gellman, S.H.,Porotto, M.,Moscona, A.
Dual Inhibition of Human Parainfluenza Type 3 and Respiratory Syncytial Virus Infectivity with a Single Agent.
J.Am.Chem.Soc., 141:12648-12656, 2019

PubMed Abstract: Human parainfluenza virus 3 (HPIV3) and respiratory syncytial virus (RSV) cause lower respiratory infection in infants and young children. There are no vaccines for these pathogens, and existing treatments have limited or questionable efficacy. Infection by HPIV3 or RSV requires fusion of the viral and cell membranes, a process mediated by a trimeric fusion glycoprotein (F) displayed on the viral envelope. Once triggered, the pre-fusion form of F undergoes a series of conformational changes that first extend the molecule to allow for insertion of the hydrophobic fusion peptide into the target cell membrane and then refold the trimeric assembly into an energetically stable post-fusion state, a process that drives the merger of the viral and host cell membranes. Peptides derived from defined regions of HPIV3 F inhibit infection by HPIV3 by interfering with the structural transitions of the trimeric F assembly. Here we describe lipopeptides derived from the C-terminal heptad repeat (HRC) domain of HPIV3 F that potently inhibit infection by both HPIV3 and RSV. The lead peptide inhibits RSV infection as effectively as does a peptide corresponding to the RSV HRC domain itself. We show that the inhibitors bind to the N-terminal heptad repeat (HRN) domains of both HPIV3 and RSV F with high affinity. Co-crystal structures of inhibitors bound to the HRN domains of HPIV3 or RSV F reveal remarkably different modes of binding in the N-terminal segment of the inhibitor.

PubMed: 31268705
DOI: 10.1021/jacs.9b04615

実験手法

X-RAY DIFFRACTION (2.2 Å)