阿爾法病毒是重要動物和人類病原體,,而且是可以致命的,,如由蚊子傳播的Chikungunya病毒所造成的感染最近在印度和東南亞的爆發(fā)所表明的那樣。阿爾法病毒的E1 和 E2糖蛋白在這種病毒感染宿主細(xì)胞的方式中居中心地位,。形成病毒表面上尖狀物的E1/E2異二聚體在宿主細(xì)胞內(nèi)部囊泡中的微酸性條件下會分解,,E1通過與核內(nèi)體膜融合來觸發(fā)感染,。Félix Rey及其同事介紹了在中性pH值下Chikungunya病毒包膜糖蛋白的結(jié)構(gòu);Michael Rossmann及其同事介紹了另一種阿爾法病毒,、即人類“辛德畢斯熱”致病病毒的包膜糖蛋白在低pH值下的結(jié)構(gòu),。對兩種結(jié)構(gòu)所做的對比為這種融合激發(fā)是怎樣被控制的提供了線索,也指出了可能的疫苗作用目標(biāo),。(生物谷Bioon.com)
生物谷推薦原文出處:
Nature doi:10.1038/nature09546
Structural changes of envelope proteins during alphavirus fusion
Long Li,Joyce Jose,Ye Xiang,Richard J. Kuhn& Michael G. Rossmann
Alphaviruses are enveloped RNA viruses that have a diameter of about 700?? and can be lethal human pathogens1. Entry of virus into host cells by endocytosis is controlled by two envelope glycoproteins, E1 and E2. The E2–E1 heterodimers form 80 trimeric spikes on the icosahedral virus surface1, 2, 60 with quasi-three-fold symmetry and 20 coincident with the icosahedral three-fold axes arranged with T = 4 quasi-symmetry. The E1 glycoprotein has a hydrophobic fusion loop at one end and is responsible for membrane fusion3, 4. The E2 protein is responsible for receptor binding5, 6 and protects the fusion loop at neutral pH. The lower pH in the endosome induces the virions to undergo an irreversible conformational change in which E2 and E1 dissociate and E1 forms homotrimers, triggering fusion of the viral membrane with the endosomal membrane and then releasing the viral genome into the cytoplasm3, 4. Here we report the structure of an alphavirus spike, crystallized at low pH, representing an intermediate in the fusion process and clarifying the maturation process. The trimer of E2–E1 in the crystal structure is similar to the spikes in the neutral pH virus except that the E2 middle region is disordered, exposing the fusion loop. The amino- and carboxy-terminal domains of E2 each form immunoglobulin-like folds, consistent with the receptor attachment properties of E2.