THE STRUCTURE OF HUMAN RHINOVIRUS-16
THE STRUCTURE OF HUMAN RHINOVIRUS-16
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DOI：
10.1016/0969-2126(93)90008-5
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发表时间：
1993-09-15
期刊：
影响因子：
5.7
通讯作者：
ROSSMANN, MG
中科院分区：
文献类型：
--
作者：
OLIVEIRA, MA;ZHAO, R;ROSSMANN, MG
背景：鼻病毒和同源脊髓灰质炎病毒在其受体结合位点下方具有疏水口袋，其中通常包含未识别的电子密度（“口袋因子”）。某些抗病毒化合物也会结合在口袋中，取代口袋因子并抑制脱衣。然而，人鼻病毒 (HRV)14 属于使用细胞间粘附分子 1 (ICAM-1) 作为受体的主要鼻病毒组，它的口袋是空的。当抗病毒化合物结合到 HRV14 的空袋中时，袋的顶部（也是受体结合位点（峡谷）的底部）会变形，从而阻止受体附着。口袋在鼻腔感染中的作用尚不清楚。结果：我们已经以原子分辨率确定了另一种主要受体组鼻病毒血清型 HRV16 的结构。与 HRV14 不同，这些口袋包含类似于脂肪酸的电子密度，八个或更多碳原子长。抗病毒化合物WIN 56231的结合不会导致口袋变形，尽管它确实阻止了受体附着。结论：我们推测，受体与HRV16的结合只有在口袋暂时为空时才会发生，此时峡谷底有可能向下变形进入口袋。我们进一步提出，口袋因子的作用是稳定病毒从一个宿主细胞转移到下一个宿主细胞的过程，并且ICAM-1的结合将口袋捕获在空状态，从而根据脱壳所需使病毒不稳定。
Background: Rhinoviruses and the homologous polioviruses have hydrophobic pockets below their receptor-binding sites, which often contain unidentified electron density ('pocket factors'). Certain antiviral com pounds also bind in the pocket, displacing the pocket factor and inhibiting uncoating. However, human rhinovirus (HRV)14, which belongs to the major group of rhinoviruses that use intercellular adhesion molecule-1 (ICAM-1) as a receptor, has an empty pocket. When antiviral compounds bind into the empty pocket of HRV14, the roof of the pocket, which is also the floor of the receptor binding site (the canyon), is deformed, preventing receptor attachment. The role of the pocket in aral infectivity is not known.Results: We have determined the structure of HRV16, another major receptor group rhinovirus serotype, to atomic resolution. Unlike HRV14, the pockets contain electron density resembling a fatty acid, eight or more carbon atoms long. Binding of the antiviral compound WIN 56231 does not cause deformation of the pocket, although it does prevent receptor attachment.Conclusions: We conjecture that the binding of the receptor to HRV16 can occur only when the pocket is temporarily empty, when it is possible for the canyon floor to be deformed downwards into the pocket. We further propose that the role of the pocket factor is to stabilize virus in transit from one host cell to the next, and that binding of ICAM-1 traps the pocket in the empty state, destabilizing the virus as required for uncoating.