HCV IRES Captures an Actively Translating 80S Ribosome

被引：36

作者：

Yokoyama, Takeshi ^{[1
,2
]}

Machida, Kodai ^{[3
]}

Iwasaki, Wakana ^{[1
,2
]}

Shigeta, Tomoaki ^{[3
]}

Nishimoto, Madoka ^{[1
,2
]}

Takahashi, Mari ^{[1
,2
]}

Sakamoto, Ayako ^{[1
,2
]}

Yonemochi, Mayumi ^{[1
,2
]}

Harada, Yoshie ^{[4
]}

Shigematsu, Hideki ^{[2
,5
]}

Shirouzu, Mikako ^{[1
,2
]}

Tadakuma, Hisashi ^{[4
]}

Imataka, Hiroaki ^{[3
]}

Ito, Takuhiro ^{[1
,2
]}

机构：

[1] RIKEN, Ctr Biosyst Dynam Res, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[2] RIKEN, Ctr Life Sci Technol, Div Struct & Synthet Biol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[3] Univ Hyogo, Grad Sch Engn, Himeji, Hyogo 6712280, Japan

[4] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan

[5] RIKEN, SPring 8 Ctr, Life Sci Res Infrastruct Grp, Mikazuki, Hyogo 6795148, Japan

来源：

MOLECULAR CELL | 2019年 / 74卷 / 06期

基金：

日本学术振兴会;

关键词：

HEPATITIS-C-VIRUS; SINGLE-MOLECULE ANALYSIS; ENTRY SITE; INITIATION; VISUALIZATION; SYSTEM; MECHANISM;

D O I：

10.1016/j.molcel.2019.04.022

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 initiation of hepatitis C virus (HCV) genomic RNA is induced by an internal ribosome entry site (IRES). Our cryoelectron microscopy (cryo-EM) analysis revealed that the HCV IRES binds to the solvent side of the 40S platform of the capdependently translating 80S ribosome. Furthermore, we obtained the cryo-EM structures of the HCV IRES capturing the 40S subunit of the IRES-dependently translating 80S ribosome. In the elucidated structures, the HCV IRES "body," consisting of domain III except for subdomain IIIb, binds to the 40S subunit, while the "long arm," consisting of domain II, remains flexible and does not impede the ongoing translation. Biochemical experiments revealed that the cap-dependently translating ribosome becomes a better substrate for the HCV IRES than the free ribosome. Therefore, the HCV IRES is likely to efficiently induce the translation initiation of its downstream mRNA with the captured translating ribosome as soon as the ongoing translation terminates.

引用

页码：1205 / +

页数：18

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