All but the shortest polymorphic forms of the viral receptor DC-SIGNR assemble into stable homo- and heterotetramers
All but the shortest polymorphic forms of the viral receptor DC-SIGNR assemble into stable homo- and heterotetramers
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DOI：
10.1074/jbc.m602430200
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发表时间：
2006-06-16
影响因子：
4.8
通讯作者：
Drickamer, Kurt
中科院分区：
文献类型：
--
作者：
Guo, Yuan;Atkinson, Claire E.;Drickamer, Kurt
影响内皮受体DC-SIGNR（树突状细胞特异性细胞间粘附分子-3-抓取非整合素相关蛋白）细胞外颈区长度的多态性与包膜病毒感染易感性的差异有关。我们已经表征了这些多态性对DC-SIGNR形成四聚体的能力的影响，所述四聚体含有结合病毒包膜糖蛋白所需的糖结合位点簇。化学交联和分析超离心实验已被用来表明，只有最小形式的DC-SIGNR是有缺陷的同源四聚体组装。一种新的亲和标记方法已被用来证明，与以前的推测相反，异源四聚体可以有效地从不同长度的DC-SIGNR多肽组装。异源四聚体是稳定的，并且可以在用多种形式的DC-SIGNR转染的成纤维细胞中检测到。这些结果为解释多态性影响与病毒相互作用的方式提供了分子基础。
Polymorphisms that affect the length of the extracellular neck region of the endothelial receptor DC-SIGNR (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related protein) have been linked to differences in susceptibility to infection by enveloped viruses. We have characterized the effects of these polymorphisms on the ability of DC-SIGNR to form tetramers containing the clusters of sugar-binding sites needed for binding to viral envelope glycoproteins. Chemical cross-linking and analytical ultracentrifugation experiments have been used to show that only the smallest form of DC-SIGNR is defective in homotetramer assembly. A novel affinity-tagging approach has been employed to demonstrate that, contrary to previous speculation, heterotetramers can be assembled efficiently from DC-SIGNR polypeptides of different lengths. The heterotetramers are stable and can be detected in fibroblasts transfected with multiple forms of DC-SIGNR. These results provide a molecular basis for interpreting the way polymorphisms affect interactions with viruses.