Seet B T, Singh R, Paavola C, Lau E K, Handel T M, McFadden G
Viral Immunology & Pathogenesis Laboratories, John P. Robarts Research Institute, 1400 Western Road, Room 133, London, ON, Canada N6G 2V4.
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9008-13. doi: 10.1073/pnas.171069398. Epub 2001 Jul 24.
Poxviruses express a family of secreted proteins that bind with high affinity to chemokines and antagonize the interaction with their cognate G protein-coupled receptors (GPCRs). These viral inhibitors are novel in structure and, unlike cellular chemokine receptors, are able to specifically interact with most, if not all, CC-chemokines. We therefore sought to define the structural features of CC-chemokines that facilitate this broad-spectrum interaction. Here, we identify the residues present on human monocyte chemoattractant protein-1 (MCP-1) that are required for high-affinity interaction with the vaccinia virus 35-kDa CC-chemokine binding protein (VV-35kDa). Not only do these residues correspond to those required for interaction with the cognate receptor CCR2b but they are also conserved among many CC-chemokines. Thus, the results provide a structural basis for the ability of VV-35kDa to promiscuously recognize CC-chemokines and block binding to their receptors.
痘病毒表达一类分泌蛋白，这类蛋白能与趋化因子高亲和力结合，并拮抗趋化因子与其同源G蛋白偶联受体（GPCR）的相互作用。这些病毒抑制剂结构新颖，与细胞趋化因子受体不同，它们能够特异性地与大多数（即便不是全部）CC趋化因子相互作用。因此，我们试图确定有助于这种广谱相互作用的CC趋化因子的结构特征。在此，我们鉴定了人单核细胞趋化蛋白-1（MCP-1）上与痘苗病毒35 kDa CC趋化因子结合蛋白（VV-35kDa）进行高亲和力相互作用所需的残基。这些残基不仅与与同源受体CCR2b相互作用所需的残基相对应，而且在许多CC趋化因子中也是保守的。因此，这些结果为VV-35kDa混杂识别CC趋化因子并阻断其与受体结合的能力提供了结构基础。
