中国科学院George F. Gao课题组取得一项研究成果。他们的研究揭示了关节炎性甲病毒受体MXRA8与基孔肯雅病毒包膜蛋白结合的分子基础。 该研究于2019年5月9日发表在国际一流学术期刊《细胞》杂志上。

课题组报道了小鼠mxra8、人mxra8与基孔肯雅病毒E蛋白复合物的晶体结构以及人mxra8和基孔肯雅病毒样颗粒的冷冻电子显微镜结构。MXRA8有两个具有独特拓扑结构的类Ig结构域。这种受体结合在病毒粒子表面E蛋白刺突的两个原聚体之间的“峡谷”上。两个结合位置接触面上的原子细节表明，MXRA8的两个结构域和铰链区都与来自两个原聚体的基孔肯雅病毒E1-E2氨基酸残基发生了相互作用。值得注意的是，MXRA8的茎部区域对基孔肯雅病毒的入侵至关重要。这一发现提供了重要的信息，以发展治疗对策，来对付这些关节炎性α病毒。

据介绍，关节炎性甲病毒，如基孔肯雅病毒（chikungunyavirus，chikv），在世界范围内引起严重的衰弱性风湿性疾病，导致严重的发病率和经济损失。最近，MXRA8被报道为一种病毒的入侵受体。

附：英文原文
 

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

Author: Hao Song, Zhennan Zhao, Yan Chai, Jianxun Qi, Feng Gao, George F. Gao

Issue&Volume: May 09, 2019

Abstract: 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.

DOI: https://doi.org/10.1016/j.cell.2019.04.008

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30394-0