华盛顿大学医学院Daved H. Fremont研究小组，揭示了基孔肯雅病毒与Mxra8受体复合物的冷冻电镜结构。 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。

该研究团队提出了Mxra8的2.2Å分辨率的x射线晶体结构及冷冻电子显微镜重建的Mxra8与基孔肯雅(CHIKV)病毒样颗粒和感染性病毒结合的复合物4至5Å分辨率的晶体结构。Mxra8胞外域包含两个可以发生链交换的ig样结构域，它们以独特的二硫键连接的头对头方式排列。Mxra8通过楔入由一个三聚体刺突中的两个相邻CHIKV E2-E1异二聚体产生的缝隙并与相邻的刺突接合而进行结合。在完全成熟的病毒样颗粒（VLP）中能观察到两种结合模式，其中一种是Mxra8结合，具有独特的接触位点。只有在感染性CHIKV形成的复合物中能观察到高亲和力结合模式，因为病毒成熟和E3占位似乎影响受体结合位点的使用。该研究为Mxra8如何与CHIKV结合提供了新的见解，并为开发甲病毒侵入抑制剂提供了一条途径。

据介绍，MXRA8是多种致关节炎性甲病毒的受体，可导致人体的衰弱性急性和慢性肌肉骨骼疾病。

附：英文原文

Title: Cryo-EM Structure of Chikungunya Virus in Complex with the Mxra8 Receptor

Author: Katherine Basore, Arthur S. Kim, Christopher A. Nelson, Rong Zhang, Brittany K. Smith, Carla Uranga, Lo Vang, Ming Cheng, Michael L. Gross, Jonathan Smith, Michael S. Diamond, Daved H. Fremont

Issue&Volume: Jun 13, 2019 Volume 177Issue 7

Abstract: Mxra8 is a receptor for multiple arthritogenic alphaviruses that cause debilitating acute and chronic musculoskeletal disease in humans. Herein, we present a 2.2 resolution X-ray crystal structure of Mxra8 and 4 to 5 resolution cryo-electron microscopy reconstructions of Mxra8 bound to chikungunya (CHIKV) virus-like particles and infectious virus. The Mxra8 ectodomain contains two strand-swapped Ig-like domains oriented in a unique disulfide-linked head-to-head arrangement. Mxra8 binds by wedging into a cleft created by two adjacent CHIKV E2-E1 heterodimers in one trimeric spike and engaging a neighboring spike. Two binding modes are observed with the fully mature VLP, with one Mxra8 binding with unique contacts. Only the high-affinity binding mode was observed in the complex with infectious CHIKV, as viral maturation and E3 occupancy appear to influence receptor binding-site usage. Our studies provide insight into how Mxra8 binds CHIKV and creates a path for developing alphavirus entry inhibitors.

DOI: https://doi.org/10.1016/j.cell.2019.04.006

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30392-7