The Domain 2 of the HCV NS5A Protein Is Intrinsically Unstructured

被引：41

作者：

Hanoulle, Xavier ^{[1
]}

Badillo, Aurelie ^{[2
]}

Verdegem, Dries ^{[1
]}

Penin, Francois ^{[2
]}

Lippens, Guy ^{[1
]}

机构：

[1] Univ Lille 1 Sci & Technol, Unite Glycobiol Struct & Fonct, CNRS, UMR 8576,IFR 147, F-59655 Villeneuve Dascq, France

[2] Univ Lyon, Inst Biol & Chim Prot, CNRS, UMR 5086,IFR BioSci Gerland Lyon Sud 128, F-69397 Lyon, France

来源：

PROTEIN AND PEPTIDE LETTERS | 2010年 / 17卷 / 08期

关键词：

Hepatitis C Virus; NS5A; Domain; 2; unstructured; NMR; Circular dichroism; HEPATITIS-C-VIRUS; RNA REPLICATION; 5A PROTEIN; IDENTIFICATION; SENSITIVITY; POLYMERASE; INFECTION; REGION; C-13;

D O I：

10.2174/092986610791498920

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We present here our current understanding of the NS5A-D2 domain of the hepatitis C virus. Whereas this protein domain is globally unstructured as assessed by macroscopic techniques such as size exclusion chromatography, circular dichroism and homonuclear NMR spectroscopy, high resolution triple resonance spectroscopy allows the identification of a small region of residual structure. This region corresponds moreover to the most conserved sequence over the different genotypes of the virus, underscoring its functional importance. We show that it forms an anchoring point for the host cell cyclophilin prolyl cis/trans isomerase, providing a molecular basis for the use of cyclophilin inhibitors in an antiviral strategy.

引用

页码：1012 / 1018

页数：7

共 31 条

[21]

Polyak Stephen J, 2003, Clin Liver Dis, V7, P67, DOI 10.1016/S1089-3261(02)00075-2

[22]

Romero P, 2001, PROTEINS, V42, P38, DOI 10.1002/1097-0134(20010101)42:1<38::AID-PROT50>3.0.CO

[23]

2-3

[24] From words to literature in structural proteomics [J].

Sali, A ;

Glaeser, R ;

Earnest, T ;

Baumeister, W .

NATURE, 2003, 422 (6928) :216-225

[25] Hepatitis C virus RNA polymerase and NS5A complex with a SNARE-like protein [J].

Tu, H ;

Gao, L ;

Shi, ST ;

Taylor, DR ;

Yang, T ;

Mircheff, AK ;

Wen, YM ;

Gorbalenya, AE ;

Hwang, SB ;

Lai, MMC .

VIROLOGY, 1999, 263 (01) :30-41

[26] Graphical interpretation of Boolean operators for protein NMR assignments [J].

Verdegem, Dries ;

Dijkstra, Klaas ;

Hanoulle, Xavier ;

Lippens, Guy .

JOURNAL OF BIOMOLECULAR NMR, 2008, 42 (01) :11-21

[27] Production of infectious hepatitis C virus in tissue culture from a cloned viral genome [J].

Wakita, T ;

Pietschmann, T ;

Kato, T ;

Date, T ;

Miyamoto, M ;

Zhao, ZJ ;

Murthy, K ;

Habermann, A ;

Kräusslich, HG ;

Mizokami, M ;

Bartenschlager, R ;

Liang, TJ .

NATURE MEDICINE, 2005, 11 (07) :791-796

[28] Identification of FBL2 as a geranylgeranylated required for hepatitis C cellular protein virus RNA replication [J].

Wang, CF ;

Gale, M ;

Keller, BC ;

Huang, H ;

Brown, MS ;

Goldstein, JL ;

Ye, J .

MOLECULAR CELL, 2005, 18 (04) :425-434

[29] Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase [J].

Watashi, K ;

Ishii, N ;

Hijikata, M ;

Inoue, D ;

Murata, T ;

Miyanari, Y ;

Shimotohno, K .

MOLECULAR CELL, 2005, 19 (01) :111-122

[30]

WISHART DS, 1994, J BIOMOL NMR, V4, P171

← 1 2 3 4 →