Molecular Basis of Arthritogenic Alphavirus Receptor MXRA8 Binding to Chikungunya Virus Envelope Protein.
MXRA8
adhesion molecule
arthritogenic alphavirus
chikungunya virus
recepor binding
virus entry
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
13 06 2019
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.e12Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.