Dissection of a retrovirus envelope protein reveals structural similarity to influenza hemagglutinin
Dissection of a retrovirus envelope protein reveals structural similarity to influenza hemagglutinin
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DOI：
10.1016/s0960-9822(95)00275-2
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发表时间：
1995-12-01
期刊：
影响因子：
9.2
通讯作者：
Kim, PS
中科院分区：
文献类型：
--
作者：
Fass, D;Kim, PS
背景资料：逆转录病毒包膜蛋白的氨基酸序列含有“4-3疏水重复”，其中疏水氨基酸间隔为每四个残基，然后每三个残基，形成卷曲螺旋的序列的特征。4-3疏水重复序列位于逆转录病毒包膜蛋白的跨膜亚基（TM）中，与融合肽相邻，这是一个在膜融合过程中插入宿主双层的区域。在流感血凝素蛋白质的类似位置中的4-3疏水重复区被募集以在构象变化至可融合状态期间延伸三链卷曲螺旋。为了确定逆转录病毒TM亚基的构象和4-3疏水重复序列的作用，我们构建了Moloney小鼠白血病病毒（MMLV）包膜蛋白的可溶性肽模型。如预测的，α-螺旋片段跨越4-3重复。一个富含半胱氨酸的区域羧基末端的4-3重复赋予显着增加的稳定性，并显示一个独特的二硫键patterns.Conclusions：我们的研究结果表明，MMLV TM亚基可以折叠成一个稳定的和不同的物种在没有受体结合的“表面”共亚基（SU）的包膜复合物。由于SU亚基很容易从病毒表面脱落，我们得出结论，TM亚基结构形成了MMLV膜融合机制的核心，并且这种结构，像流感血凝素的融合活性构象一样，包含与融合肽相邻的三链卷曲螺旋。
Background: The amino-acid sequences of retroviral envelope proteins contain a '4-3 hydrophobic repeat', with hydrophobic amino acids spaced every four and then every three residues, characteristic of sequences that form coiled coils. The 4-3 hydrophobic repeat is located in the transmembrane subunit (TM) of the retroviral envelope protein, adjacent to the fusion peptide, a region that inserts into the host bilayer during the membrane-fusion process. A 4-3 hydrophobic repeat region in an analogous position of the influenza hemagglutinin protein is recruited to extend a three-stranded coiled coil during the conformational change to the fusion-competent state. To determine the conformation of the retroviral TM subunit and the role of the 4-3 hydrophobic repeat, we constructed soluble peptide models of the envelope protein of Moloney murine leukemia virus (MMLV).Results: The region of the MMLV TM protein external to the lipid envelope (the ectodomain) contains a stably folded, trimeric, protease-resistant core. As predicted, an alpha-helical segment spans the 4-3 repeat. A cysteine-rich region carboxy-terminal to the 4-3 repeat confers a dramatic increase in stability and displays a unique disulfide bonding pattern.Conclusions: Our results demonstrate that the MMLV TM subunit can fold into a stable and distinct species in the absence of the receptor-binding 'surface' co-subunit (SU) of the envelope complex. As the SU subunit is readily shed fi-om the surface of the virus, we conclude that the TM subunit structure forms the core of the MMLV membrane-fusion machinery, and that this structure, like the fusion-active conformation of influenza hemagglutinin, contains a three-stranded coiled coil adjacent to the fusion peptide.