Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR
Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR
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DOI：
10.1126/science.286.5444.1579
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发表时间：
1999-11-19
期刊：
影响因子：
56.9
通讯作者：
Flanagan, JM
中科院分区：
文献类型：
--
作者：
Bewley, MC;Springer, K;Flanagan, JM
已知病毒颗粒与特定宿主细胞表面受体的结合是感染中的必要步骤，尽管这些相互作用的分子基础还没有很好地表征。晶体结构的腺病毒纤维结域在复杂的结构域I的人细胞受体，科萨基和腺病毒受体（CAR），在这里提出。表面暴露的旋钮上的环接触CAR的一面，形成高亲和力复合物。相互作用表面之间的拓扑结构失配产生界面溶剂填充的空腔和通道，其可以是抗病毒药物治疗的靶点。该结构确定了结合特异性的关键决定因素，这可能提示了修改基于腺病毒的基因治疗载体的向性的方法。
Binding of virus particles to specific host cell surface receptors is known to be an obligatory step in infection even though the molecular basis for these interactions is not well characterized. The crystal structure of the adenovirus fiber knob domain in complex with domain I of its human cellular receptor, coxsackie and adenovirus receptor (CAR), is presented here. Surface-exposed Loops on knob contact one face of CAR, forming a high-affinity complex. Topology mismatches between interacting surfaces create interfacial solvent-filled cavities and channels that may be targets for antiviral drug therapy. The structure identifies key determinants of binding specificity, which may suggest ways to modify the tropism of adenovirus-based gene therapy vectors.