1R7C

NMR structure of the membrane anchor domain (1-31) of the nonstructural protein 5A (NS5A) of hepatitis C virus (Minimized average structure, Sample in 50% tfe)

1R7C の概要

• エントリーDOI: 10.2210/pdb1r7c/pdb
• 関連するPDBエントリー: 1R7D 1R7E 1R7F 1R7G
• NMR情報: BMRB: 5978
• 分子名称: Genome polyprotein (1 entity in total)
• 機能のキーワード: membrane anchor domain, hcv ns5a protein, membrane protein
• 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 (By similarity). 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. Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein. RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): P27958
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3770.42

構造登録者

Penin, F.,Brass, V.,Appel, N.,Ramboarina, S.,Montserret, R.,Ficheux, D.,Blum, H.E.,Bartenschlager, R.,Moradpour, D. (登録日: 2003-10-21, 公開日: 2004-08-10, 最終更新日: 2024-05-22)

主引用文献

Penin, F.,Brass, V.,Appel, N.,Ramboarina, S.,Montserret, R.,Ficheux, D.,Blum, H.E.,Bartenschlager, R.,Moradpour, D.
Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A.
J.Biol.Chem., 279:40835-40843, 2004

PubMed Abstract: Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a membrane-associated, essential component of the viral replication complex. Here, we report the three-dimensional structure of the membrane anchor domain of NS5A as determined by NMR spectroscopy. An alpha-helix extending from amino acid residue 5 to 25 was observed in the presence of different membrane mimetic media. This helix exhibited a hydrophobic, Trprich side embedded in detergent micelles, while the polar, charged side was exposed to the solvent. Thus, the NS5A membrane anchor domain forms an in-plane amphipathic alpha-helix embedded in the cytosolic leaflet of the membrane bilayer. Interestingly, mutations affecting the positioning of fully conserved residues located at the cytosolic surface of the helix impaired HCV RNA replication without interfering with the membrane association of NS5A. In conclusion, the NS5A membrane anchor domain constitutes a unique platform that is likely involved in specific interactions essential for the assembly of the HCV replication complex and that may represent a novel target for antiviral intervention.

PubMed: 15247283
DOI: 10.1074/jbc.M404761200

実験手法

SOLUTION NMR