Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins
Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins
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DOI：
10.1073/pnas.96.8.4319
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发表时间：
1999-04-13
影响因子：
11.1
通讯作者：
Poumbourios, P
中科院分区：
文献类型：
--
作者：
Kobe, B;Center, RJ;Poumbourios, P
逆转录病毒进入细胞依赖于包膜糖蛋白，由此受体与表面暴露的亚基结合触发跨膜蛋白（TM）亚基的膜融合。我们在2.5埃分辨率下测定了gp 21胞外结构域的晶体结构，gp 21是来自人T细胞白血病病毒1型的TM。将gp 21片段结晶为麦芽糖结合蛋白嵌合体，并通过分子置换的方法将麦芽糖结合蛋白结构域用于解决初始相。gp 21的结构包括一个N-末端三聚体卷曲螺旋，一个相邻的二硫键环，稳定链逆转，和一个C-末端序列，结构上不同于HIV 1型/猴免疫缺陷病毒gp 41，以延长的反平行方式包装对线圈。gp 21结构与其他逆转录病毒TM的结构的比较，对比了卷曲螺旋形成区和相邻二硫键环的保守性与C-末端胞外域区段的可变性。该结构指出这些特征已经进化以使逆转录病毒TM具有双重作用：保守的融合功能和将不同的表面暴露的亚基结构锚到病毒体包膜和感染细胞表面的能力。gp 21的结构意味着N-末端融合肽非常接近C-末端跨膜结构域，可能代表融合后构象。
Retroviral entry into cells depends on envelope glycoproteins, whereby receptor binding to the surface-exposed subunit triggers membrane fusion by the transmembrane protein (TM) subunit. We determined the crystal structure at 2.5-Angstrom resolution of the ectodomain of gp21, the TM from human T cell leukemia virus type 1. The gp21 fragment was crystallized as a maltose-binding protein chimera, and the maltose-binding protein domain was used to solve the initial phases by the method of molecular replacement. The structure of gp21 comprises an N-terminal trimeric coiled coil, an adjacent disulfide-bonded loop that stabilizes a chain reversal, and a C-terminal sequence structurally distinct from HIV type 1/simian immunodeficiency virus gp41 that packs against the coil in an extended antiparallel fashion. Comparison of the gp21 structure with the structures of other retroviral TMs contrasts the conserved nature of the coiled coil-forming region and adjacent disulfide-bonded loop with the variable nature of the C-terminal ectodomain segment. The structure points to these features having evolved to enable the dual roles of retroviral TMs: conserved fusion function and an ability to anchor diverse surface-exposed subunit structures to the virion envelope and infected cell surface. The structure of gp21 implies that the N-terminal fusion peptide is in close proximity to the C-terminal transmembrane domain and likely represents a postfusion conformation.