Crystal structure of 2C helicase from enterovirus 71

Science Advances
Hongxin GuanSheng Cui

Abstract

Enterovirus 71 (EV71) is the major pathogen responsible for outbreaks of hand, foot, and mouth disease. EV71 nonstructural protein 2C participates in many critical events throughout the virus life cycle; however, its precise role is not fully understood. Lack of a high-resolution structure made it difficult to elucidate 2C activity and prevented inhibitor development. We report the 2.5 Å-resolution crystal structure of the soluble part of EV71 2C, containing an adenosine triphosphatase (ATPase) domain, a cysteine-rich zinc finger with an unusual fold, and a carboxyl-terminal helical domain. Unlike other AAA+ ATPases, EV71 2C undergoes a carboxyl terminus-mediated self-oligomerization, which is dependent on a specific interaction between the carboxyl-terminal helix of one monomer and a deep pocket formed between the ATPase and the zinc finger domains of the neighboring monomer. The carboxyl terminus-mediated self-oligomerization is fundamental to 2C ATPase activity and EV71 replication. Our findings suggest a strategy for inhibition of enterovirus replication by disruption of the self-oligomerization interface of 2C.

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Citations

Apr 8, 2018·Nature Reviews. Microbiology·Jim BaggenFrank J M van Kuppeveld
Sep 20, 2018·PLoS Pathogens·Hongxin GuanSheng Cui
Mar 9, 2018·Frontiers in Microbiology·Jingjing YuanLingxiang Mao
Dec 16, 2018·Virologica Sinica·Huiqiang Wang, Yuhuan Li
Jan 1, 2021·Frontiers in Microbiology·Shao-Hua WangJuan Du
Apr 3, 2020·Antiviral Research·Roberto ManganaroAndrea Brancale
Mar 23, 2021·Emerging Microbes & Infections·Pei Yi AngSylvie Alonso
Jul 29, 2021·Open Biology·Aušra DomanskaSarah J Butcher
Jul 16, 2019·ACS Infectious Diseases·Lisa BauerFrank J M van Kuppeveld
May 1, 2020·ACS Infectious Diseases·Yanmei HuJun Wang

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Methods Mentioned

BETA
PISA
size exclusion chromatography
x-ray scattering

Software Mentioned

ATSAS
SHLEXC
Phaser
PISA
- MR
SAS
Coot

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