Molecular Basis of Arthritogenic Alphavirus Receptor MXRA8 Binding to Chikungunya Virus Envelope Protein.


Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
13 06 2019
Historique:
received: 15 10 2018
revised: 07 02 2019
accepted: 01 04 2019
pubmed: 14 5 2019
medline: 11 3 2020
entrez: 14 5 2019
Statut: ppublish

Résumé

Arthritogenic alphaviruses, such as Chikungunya virus (CHIKV), cause severe and debilitating rheumatic diseases worldwide, resulting in severe morbidity and economic costs. Recently, MXRA8 was reported as an entry receptor. Here, we present the crystal structures of the mouse MXRA8, human MXRA8 in complex with the CHIKV E protein, and the cryo-electron microscopy structure of human MXRA8 and CHIKV virus-like particle. MXRA8 has two Ig-like domains with unique structural topologies. This receptor binds in the "canyon" between two protomers of the E spike on the surface of the virion. The atomic details at the interface between the two binding entities reveal that both the two domains and the hinge region of MXRA8 are involved in interaction with CHIKV E1-E2 residues from two protomers. Notably, the stalk region of MXRA8 is critical for CHIKV virus entry. This finding provides important information regarding the development of therapeutic countermeasures against those arthritogenic alphaviruses.

Identifiants

pubmed: 31080063
pii: S0092-8674(19)30394-0
doi: 10.1016/j.cell.2019.04.008
pii:
doi:

Substances chimiques

Membrane Proteins 0
Viral Envelope Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1714-1724.e12

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Hao Song (H)

Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.

Zhennan Zhao (Z)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.

Yan Chai (Y)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Xiyue Jin (X)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.

Changyao Li (C)

College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

Fei Yuan (F)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Sheng Liu (S)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.

Zhengrong Gao (Z)

Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.

Haiyuan Wang (H)

College of Animal Sciences and Technology, Guangxi University, Nanning 530004, China.

Jian Song (J)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Leonardo Vazquez (L)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; National Institute of Science and Technology for Innovation on Diseases of Neglected Populations (INCT-IDPN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Rio de Janeiro 21040-361, Brazil.

Yanfang Zhang (Y)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.

Shuguang Tan (S)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Carlos M Morel (CM)

National Institute of Science and Technology for Innovation on Diseases of Neglected Populations (INCT-IDPN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Rio de Janeiro 21040-361, Brazil.

Jinghua Yan (J)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Yi Shi (Y)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; CAS Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.

Jianxun Qi (J)

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.

Feng Gao (F)

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China; Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: gaofeng@tib.cas.cn.

George F Gao (GF)

Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China; CAS Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China; Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address: gaof@im.ac.cn.

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