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TitleMolecular Basis of Arthritogenic Alphavirus Receptor MXRA8 Binding to Chikungunya Virus Envelope Protein.
Journal, issue, pagesCell, Vol. 177, Issue 7, Page 1714-1724.e12, Year 2019
Publish dateJun 13, 2019
AuthorsHao Song / Zhennan Zhao / Yan Chai / Xiyue Jin / Changyao Li / Fei Yuan / Sheng Liu / Zhengrong Gao / Haiyuan Wang / Jian Song / Leonardo Vazquez / Yanfang Zhang / Shuguang Tan / Carlos M Morel / Jinghua Yan / Yi Shi / Jianxun Qi / Feng Gao / George F Gao /
PubMed AbstractArthritogenic alphaviruses, such as Chikungunya virus (CHIKV), cause severe and debilitating rheumatic diseases worldwide, resulting in severe morbidity and economic costs. Recently, MXRA8 was ...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.
External linksCell / PubMed:31080063
MethodsEM (single particle) / X-ray diffraction
Resolution2.4 - 8.9 Å
Structure data

EMDB-9857:
Cryo-EM structure of Chikungunya VLP in complex with its receptor MXRA8
Method: EM (single particle) / Resolution: 8.9 Å

PDB-6jo7:
Crystal structure of mouse MXRA8
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-6jo8:
The complex structure of CHIKV envelope glycoprotein bound to human MXRA8
Method: X-RAY DIFFRACTION / Resolution: 3.495 Å

Chemicals

ChemComp-HOH:
WATER / Water

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • chikungunya virus
  • mus musculus (house mouse)
  • homo sapiens (human)
KeywordsPROTEIN BINDING / Arthritogenic alphaviruses / receptor / virus entry / Chikungunya virus / VIRAL PROTEIN / MXRA8

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