Structural rearrangements in the membrane penetration protein of a non-enveloped virus
Structural rearrangements in the membrane penetration protein of a non-enveloped virus
复制标题
DOI：
10.1038/nature02836
复制
发表时间：
2004-08-26
期刊：
影响因子：
64.8
通讯作者：
Harrison, SC
中科院分区：
文献类型：
--
作者：
Dormitzer, PR;Nason, EB;Harrison, SC
无包膜病毒颗粒（缺乏脂质双层膜的那些）必须突破靶宿主细胞的膜才能进入其细胞质。到目前为止，这一膜渗透步骤的分子机制还无法进行结构分析。刺突蛋白VP 4是轮状病毒进入器官的主要成分，轮状病毒是一种无包膜病毒，可引起胃肠炎，每年导致440，000名儿童死亡（1）。VP 4的胰蛋白酶裂解通过触发重排使VP 4刺突硬化来引发病毒进入（2）。我们已经确定了晶体结构，在3.2埃的分辨率，从病毒体项目的VP 4的主要部分。晶体结构揭示了卷曲螺旋稳定的三聚体。在胰蛋白酶引发的病毒体的电子冷冻显微镜中，类似于12埃分辨率的图像重建中，将这种结构与两倍聚集的VP 4刺突进行比较，表明VP 4也经历了第二次重排，其中寡聚体重组，每个亚基折叠回自身，将潜在的膜相互作用肽从刺突的一端转移到另一端。这种重排类似于包膜病毒的膜融合蛋白的构象转变（3-6）。
Non-enveloped virus particles (those that lack a lipid-bilayer membrane) must breach the membrane of a target host cell to gain access to its cytoplasm. So far, the molecular mechanism of this membrane penetration step has resisted structural analysis. The spike protein VP4 is a principal component in the entry apparatus of rotavirus, a non-enveloped virus that causes gastroenteritis and kills 440,000 children each year(1). Trypsin cleavage of VP4 primes the virus for entry by triggering a rearrangement that rigidifies the VP4 spikes(2). We have determined the crystal structure, at 3.2 Angstrom resolution, of the main part of VP4 that projects from the virion. The crystal structure reveals a coiled-coil stabilized trimer. Comparison of this structure with the two-fold clustered VP4 spikes in a similar to12 Angstrom resolution image reconstruction from electron cryomicroscopy of trypsin-primed virions shows that VP4 also undergoes a second rearrangement, in which the oligomer reorganizes and each subunit folds back on itself, translocating a potential membrane-interaction peptide from one end of the spike to the other. This rearrangement resembles the conformational transitions of membrane fusion proteins of enveloped viruses(3-6).