2LIF

Solution Structure of KKGF

2LIF の概要

• エントリーDOI: 10.2210/pdb2lif/pdb
• NMR情報: BMRB: 17891
• 分子名称: Core protein p21 (1 entity in total)
• 機能のキーワード: signal peptide, e1 envelope protein, core protein, transmembrane, membrane protein, viral protein
• 由来する生物種: Hepatitis C virus JFH-1 (HCV)
• 細胞内の位置: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein (By similarity). Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein. Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (Probable). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): Q99IB8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2881.54

構造登録者

Montserret, R.,Penin, F. (登録日: 2011-08-29, 公開日: 2012-07-11, 最終更新日: 2024-05-15)

主引用文献

Oehler, V.,Filipe, A.,Montserret, R.,da Costa, D.,Brown, G.,Penin, F.,McLauchlan, J.
Structural analysis of hepatitis C virus core-e1 signal Peptide and requirements for cleavage of the genotype 3a signal sequence by signal Peptide peptidase.
J.Virol., 86:7818-7828, 2012

PubMed Abstract: The maturation of the hepatitis C virus (HCV) core protein requires proteolytic processing by two host proteases: signal peptidase (SP) and the intramembrane-cleaving protease signal peptide peptidase (SPP). Previous work on HCV genotype 1a (GT1a) and GT2a has identified crucial residues required for efficient signal peptide processing by SPP, which in turn has an effect on the production of infectious virus particles. Here we demonstrate that the JFH1 GT2a core-E1 signal peptide can be adapted to the GT3a sequence without affecting the production of infectious HCV. Through mutagenesis studies, we identified crucial residues required for core-E1 signal peptide processing, including a GT3a sequence-specific histidine (His) at position 187. In addition, the stable knockdown of intracellular SPP levels in HuH-7 cells significantly affects HCV virus titers, further demonstrating the requirement for SPP for the maturation of core and the production of infectious HCV particles. Finally, our nuclear magnetic resonance (NMR) structural analysis of a synthetic HCV JFH1 GT2a core-E1 signal peptide provides an essential structural template for a further understanding of core processing as well as the first model for an SPP substrate within its membrane environment. Our findings give deeper insights into the mechanisms of intramembrane-cleaving proteases and the impact on viral infections.

PubMed: 22593157
DOI: 10.1128/JVI.00457-12

実験手法

SOLUTION NMR