Crystal Structure of the HCV IRES Central Domain Reveals Strategy for Start-Codon Positioning

被引：88

作者：

Berry, Katherine E. ^{[1
]}

Waghray, Shruti ^{[1
]}

Mortimer, Stefanie A. ^{[2
]}

Bai, Yun ^{[2
]}

Doudna, Jennifer A. ^{[1
,2
,3
,4
]}

机构：

[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[3] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA

[4] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA

来源：

STRUCTURE | 2011年 / 19卷 / 10期

基金：

美国国家卫生研究院;

关键词：

HEPATITIS-C-VIRUS; RIBOSOME-ENTRY SITE; SWINE-FEVER VIRUS; 5' UNTRANSLATED REGION; TRANSLATION INITIATION; RNA STRUCTURE; INTERNAL INITIATION; PSEUDOKNOT; ELEMENT; BINDING;

D O I：

10.1016/j.str.2011.08.002

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：

Translation of hepatitis C viral proteins requires an internal ribosome entry site (IRES) located in the 5' untranslated region of the viral mRNA. The core domain of the hepatitis C virus (HCV) IRES contains a four-way helical junction that is integrated within a predicted pseudoknot. This domain is required for positioning the mRNA start codon correctly on the 40S ribosomal subunit during translation initiation. Here, we present the crystal structure of this RNA, revealing a complex double-pseudoknot fold that establishes the alignment of two helical elements on either side of the four-helix junction. The conformation of this core domain constrains the open reading frame's orientation for positioning on the 40S ribosomal subunit. This structure, representing the last major domain of HCV-like IRESs to be determined at near-atomic resolution, provides the basis for a comprehensive cryoelectron microscopy-guided model of the intact HCV IRES and its interaction with 40S ribosomal subunits.

引用

页码：1456 / 1466

页数：11

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