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针对一种变异的细胞间黏附分子-1(ICAM-1)受体分子的鼻病毒血清型鉴别。

Discrimination among rhinovirus serotypes for a variant ICAM-1 receptor molecule.

作者信息

Xiao Chuan, Tuthill Tobias J, Bator Kelly Carol M, Challinor Lisa J, Chipman Paul R, Killington Richard A, Rowlands David J, Craig Alister, Rossmann Michael G

机构信息

Department of Biological Sciences, Purdue University, 915 W. State St., West Layfayette, IN 47909-2054, USA.

出版信息

J Virol. 2004 Sep;78(18):10034-44. doi: 10.1128/JVI.78.18.10034-10044.2004.

Abstract

Intercellular adhesion molecule 1 (ICAM-1) is the cellular receptor for the major group of human rhinovirus serotypes, including human rhinovirus 14 (HRV14) and HRV16. A naturally occurring variant of ICAM-1, ICAM-1Kilifi, has altered binding characteristics with respect to different HRV serotypes. HRV14 binds to ICAM-1 only transiently at physiological temperatures but forms a stable complex with ICAM-1Kilifi. Conversely, HRV16 forms a stable complex with ICAM-1 but does not bind to ICAM-1Kilifi. The three-dimensional structures of HRV14 and HRV16, complexed with ICAM-1, and the structure of HRV14, complexed with ICAM-1Kilifi, have been determined by cryoelectron microscopy (cryoEM) image reconstruction to a resolution of approximately 10 angstroms. Structures determined by X-ray crystallography of both viruses and of ICAM-1 were fitted into the cryoEM density maps. The interfaces between the viruses and receptors contain extensive ionic networks. However, the interactions between the viruses and ICAM-1Kilifi contain one less salt bridge than between the viruses and ICAM-1. As HRV16 has fewer overall interactions with ICAM-1 than HRV14, the absence of this charge interaction has a greater impact on the binding of ICAM-1Kilifi to HRV16 than to HRV14.

摘要

细胞间黏附分子1(ICAM-1)是包括人鼻病毒14型(HRV14)和HRV16在内的主要人鼻病毒血清型的细胞受体。ICAM-1的一种天然变体ICAM-1Kilifi,在与不同HRV血清型的结合特性方面有所改变。HRV14在生理温度下仅与ICAM-1短暂结合,但与ICAM-1Kilifi形成稳定复合物。相反,HRV16与ICAM-1形成稳定复合物,但不与ICAM-1Kilifi结合。通过冷冻电子显微镜(cryoEM)图像重建确定了与ICAM-1复合的HRV14和HRV16的三维结构,以及与ICAM-1Kilifi复合的HRV14的结构,分辨率约为10埃。通过X射线晶体学确定的两种病毒和ICAM-1的结构被拟合到cryoEM密度图中。病毒与受体之间的界面包含广泛的离子网络。然而,病毒与ICAM-1Kilifi之间的相互作用比病毒与ICAM-1之间的盐桥少一个。由于HRV16与ICAM-1的总体相互作用比HRV14少,这种电荷相互作用的缺失对ICAM-1Kilifi与HRV16的结合比对HRV14的结合影响更大。

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