Alexander Jennifer M, Nelson Christopher A, van Berkel Victor, Lau Elaine K, Studts Joey M, Brett Tom J, Speck Samuel H, Handel Tracy M, Virgin Herbert W, Fremont Daved H
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Cell. 2002 Nov 1;111(3):343-56. doi: 10.1016/s0092-8674(02)01007-3.
The M3 protein encoded by murine gamma herpesvirus68 (gamma HV68) functions as an immune system saboteur by the engagement of chemoattractant cytokines, thereby altering host antiviral inflammatory responses. Here we report the crystal structures of M3 both alone and in complex with the CC chemokine MCP-1. M3 is a two-domain beta sandwich protein with a unique sequence and topology, forming a tightly packed anti-parallel dimer. The stoichiometry of the MCP-1:M3 complex is 2:2, with two monomeric chemokines embedded at distal ends of the preassociated M3 dimer. Conformational flexibility and electrostatic complementation are both used by M3 to achieve high-affinity and broad-spectrum chemokine engagement. M3 also employs structural mimicry to promiscuously sequester chemokines, engaging conservative structural elements associated with both chemokine homodimerization and binding to G protein-coupled receptors.
小鼠γ疱疹病毒68（γHV68）编码的M3蛋白通过与趋化因子细胞因子结合，充当免疫系统破坏者，从而改变宿主抗病毒炎症反应。在此，我们报告了M3单独以及与CC趋化因子MCP-1形成复合物时的晶体结构。M3是一种具有独特序列和拓扑结构的双结构域β折叠夹心蛋白，形成紧密堆积的反平行二聚体。MCP-1与M3复合物的化学计量比为2:2，两个单体趋化因子嵌入预先形成的M3二聚体的远端。M3利用构象灵活性和静电互补来实现高亲和力和广谱趋化因子结合。M3还采用结构模拟来杂乱地隔离趋化因子，与与趋化因子同二聚化和与G蛋白偶联受体结合相关的保守结构元件结合。
