Cryo-EM structure of Hepatitis C virus IRES bound to the human ribosome at 3.9-Å resolution

被引：100

作者：

Quade, Nick ^{[1
]}

Boehringer, Daniel ^{[1
]}

Leibundgut, Marc ^{[1
]}

van den Heuvel, Joop ^{[2
]}

Ban, Nenad ^{[1
]}

机构：

[1] ETH, Inst Mol Biol & Biophys, Dept Biol, CH-8093 Zurich, Switzerland

[2] Helmholtz Ctr Infect Res, Res Grp Recombinant Prot Express, D-38124 Braunschweig, Germany

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

TRANSLATION INITIATION; CRYSTAL-STRUCTURE; DOMAIN-II; EUKARYOTIC RIBOSOME; MUTATIONAL ANALYSIS; 80S RIBOSOME; ENTRY SITES; RNA; HCV; COMPLEX;

D O I：

10.1038/ncomms8646

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Hepatitis C virus (HCV), a widespread human pathogen, is dependent on a highly structured 50'-untranslated region of its mRNA, referred to as internal ribosome entry site (IRES), for the translation of all of its proteins. The HCV IRES initiates translation by directly binding to the small ribosomal subunit (40S), circumventing the need for many eukaryotic translation initiation factors required for mRNA scanning. Here we present the cryo-EM structure of the human 40S ribosomal subunit in complex with the HCV IRES at 3.9 angstrom resolution, determined by focused refinement of an 80S ribosome-HCV IRES complex. The structure reveals the molecular details of the interactions between the IRES and the 40S, showing that expansion segment 7 (ES7) of the 18S rRNA acts as a central anchor point for the HCV IRES. The structural data rationalizes previous biochemical and genetic evidence regarding the initiation mechanism of the HCV and other related IRESs.

引用

页数：9

共 53 条

[1] PHENIX: a comprehensive Python']Python-based system for macromolecular structure solution [J].

Adams, Paul D. ;

Afonine, Pavel V. ;

Bunkoczi, Gabor ;

Chen, Vincent B. ;

Davis, Ian W. ;

Echols, Nathaniel ;

Headd, Jeffrey J. ;

Hung, Li-Wei ;

Kapral, Gary J. ;

Grosse-Kunstleve, Ralf W. ;

McCoy, Airlie J. ;

Moriarty, Nigel W. ;

Oeffner, Robert ;

Read, Randy J. ;

Richardson, David C. ;

Richardson, Jane S. ;

Terwilliger, Thomas C. ;

Zwart, Peter H. .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2010, 66 :213-221

[2] The Structure of the Eukaryotic Ribosome at 3.0 Å Resolution [J].

Ben-Shem, Adam ;

de Loubresse, Nicolas Garreau ;

Melnikov, Sergey ;

Jenner, Lasse ;

Yusupova, Gulnara ;

Yusupov, Marat .

SCIENCE, 2011, 334 (6062) :1524-1529

[3] Crystal Structure of the HCV IRES Central Domain Reveals Strategy for Start-Codon Positioning [J].

Berry, Katherine E. ;

Waghray, Shruti ;

Mortimer, Stefanie A. ;

Bai, Yun ;

Doudna, Jennifer A. .

STRUCTURE, 2011, 19 (10) :1456-1466

[4] The HCV IRES pseudoknot positions the initiation codon on the 40S ribosomal subunit [J].

Berry, Katherine E. ;

Waghray, Shruti ;

Doudna, Jennifer A. .

RNA, 2010, 16 (08) :1559-1569

[5] Targeting ribosome assembly on the HCV RNA using a small RNA molecule [J].

Bhat, Prasanna ;

Gnanasundram, Sivakumar Vadivel ;

Mani, Prashant ;

Ray, Partho Sarothi ;

Sarkar, Debi P. ;

Das, Saumitra .

RNA BIOLOGY, 2012, 9 (08) :1110-1119

[6]

Blasey H. D., 1991, ANIMAL CELL CULTURE

[7] Structure of the hepatitis C virus IRES bound to the human 80S ribosome: Remodeling of the HCVIRES [J].

Boehringer, D ;

Thermann, R ;

Ostareck-Lederer, A ;

Lewis, JD ;

Stark, H .

STRUCTURE, 2005, 13 (11) :1695-1706

[8] SECONDARY STRUCTURE OF THE 5' NONTRANSLATED REGIONS OF HEPATITIS-C VIRUS AND PESTIVIRUS GENOMIC RNAS [J].

BROWN, EA ;

ZHANG, HC ;

PING, LH ;

LEMON, SM .

NUCLEIC ACIDS RESEARCH, 1992, 20 (19) :5041-5045

[9] Structure of a hepatitis C virus RNA domain in complex with a translation inhibitor reveals a binding mode reminiscent of riboswitches [J].

Dibrov, Sergey M. ;

Ding, Kejia ;

Brunn, Nicholas D. ;

Parker, Matthew A. ;

Bergdahl, B. Mikael ;

Wyles, David L. ;

Hermann, Thomas .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (14) :5223-5228

[10] Conserved functional domains and a novel tertiary interaction near the pseudoknot drive translational activity of hepatitis C virus and hepatitis C virus-like internal ribosome entry sites [J].

Easton, Laura E. ;

Locker, Nicolas ;

Lukavsky, Peter J. .

NUCLEIC ACIDS RESEARCH, 2009, 37 (16) :5537-5549

← 1 2 3 4 5 6 →