Activation of a retroviral membrane fusion protein: soluble receptor-induced liposome binding of the ALSV envelope glycoprotein.
Activation of a retroviral membrane fusion protein: soluble receptor-induced liposome binding of the ALSV envelope glycoprotein.
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DOI：
10.1083/jcb.139.6.1455
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发表时间：
1997-12-15
期刊：
影响因子：
--
通讯作者：
White JM
中科院分区：
文献类型：
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作者：
Hernandez LD;Peters RJ;Delos SE;Young JA;Agard DA;White JM
尚不清楚在中性pH下起作用的膜融合蛋白，例如人免疫缺陷病毒包膜（Env）糖蛋白和细胞内融合机器如何被激活以用于靶双层结合。我们已经使用可溶性寡聚形式的禽类逆转录病毒Env糖蛋白（API）及其受体的可溶性形式解决了这个问题。可溶性受体与API的结合诱导API在中性pH下与由磷脂酰胆碱和胆固醇组成的脂质体结合。脂质体结合仅在融合容许温度（T > 20°C）下发生，在37°C下在2至5分钟之间完成，并且对高盐、碳酸盐和尿素稳定。脂质体结合由API的跨膜亚基的胞外域介导，并且在Env融合肽中具有瓦尔至Glu取代的突变体（位于跨膜亚基的胞外域中）显示显著降低的脂质体结合。此外，在与API等效结合的条件下，不支持感染的突变受体（Zingler，K.，还有J.A.T.年轻1996. J. Virol. 70：7510-7516）不诱导显著的脂质体结合。我们的研究结果表明，禽逆转录病毒Env和其受体之间的高度特异性相互作用激活逆转录病毒糖蛋白的目标双层结合在中性pH值的低pH值激活流感血凝素几乎相同的方式。我们的研究结果进行了讨论，在中性pH值的功能的病毒和细胞融合蛋白的机制。
It is not known how membrane fusion proteins that function at neutral pH, for example the human immunodeficiency virus envelope (Env) glycoprotein and intracellular fusion machines, are activated for target bilayer binding. We have addressed this question using a soluble oligomeric form of an avian retroviral Env glycoprotein (API) and soluble forms of its receptor. Binding of soluble receptor to API induces API to bind to liposomes composed of phosphatidylcholine and cholesterol at neutral pH. Liposome binding only occurs at fusion permissive temperatures (T > 20°C), is complete between 2 to 5 min at 37°C, and is stable to high salt, carbonate, and urea. Liposome binding is mediated by the ectodomain of the transmembrane subunit of API, and a mutant with a Val to Glu substitution in the Env fusion peptide (located in the ectodomain of the transmembrane subunit) shows significantly reduced liposome binding. Moreover, under conditions of equivalent binding to API, a mutant receptor that does not support infection (Zingler, K., and J.A.T. Young. 1996. J. Virol. 70:7510–7516) does not induce significant liposome binding. Our results indicate that a highly specific interaction between an avian retroviral Env and its receptor activates the retroviral glycoprotein for target bilayer binding at neutral pH in much the same way as low pH activates the influenza hemagglutinin. Our findings are discussed in terms of the mechanisms of viral and cellular fusion proteins that function at neutral pH.