The tryptophan-rich region of HIV gp41 and the promotion of cholesterol-rich domains
The tryptophan-rich region of HIV gp41 and the promotion of cholesterol-rich domains
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DOI：
10.1021/bi0500224
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发表时间：
2005-04-12
期刊：
影响因子：
2.9
通讯作者：
Epand, RM
中科院分区：
文献类型：
--
作者：
Epand, RF;Sayer, BG;Epand, RM
N-乙酰-KWASLWNWFNITNWLWYIK-酰胺具有与HIV-1 gp41融合蛋白的膜旁区域相对应的序列。我们用差示扫描量热法、圆二色谱、荧光光谱和核磁共振研究了胆固醇是如何调节该多肽与含胆固醇膜的相互作用的。我们发现，与N-乙酰-LWYIK-酰胺相比，这种多肽将胆固醇隔离到结构域的能力较差。另一方面，对应于HIV-2和SIV gp41融合蛋白片段的N-乙酰-LASWIK-酰胺，尽管没有胆固醇识别/相互作用氨基酸共识序列(CRAC)，但在形成富含胆固醇的区域方面具有介于N-乙酰-KWASLWNWFNITNWLWYIK-酰胺和N-乙酰-LWYIK-酰胺之间的中等效力。我们认为，HIV-1和HIV-2在决定其趋向性方面对糖鞘糖脂的需求的差异与它们在生物膜上对富含胆固醇的区域的分配不同有关。
The peptide N-acetyl-KWASLWNWFNITNWLWYIK-amide has a sequence that corresponds to the juxtamembrane region of the HIV-1 gp41 fusion protein. We have studied how cholesterol modulates the interaction of this peptide with membranes containing cholesterol using differential scanning calorimetry, circular dichroism, fluorescence spectroscopy, and nuclear magnetic resonance. We find that this peptide is less able to sequester cholesterol into domains than is N-acetyl-LWYIK-amide. On the other hand, the peptide N-acetyl-LASWIK-amide, which corresponds to a segment of HIV-2 and SIV gp41 fusion proteins, has intermediate potency between N-acetyl-KWASLWNWFNITNWLWYIK-amide and N-acetyl-LWYIK-amide in forming areas enriched in cholesterol, even though it does not have a cholesterol recognition/ interaction amino acid consensus sequence (CRAC). We suggest that the difference between HIV-1 and HIV-2 in their requirements for glycosphingolipids in determining their tropism is related to their difference in partitioning to cholesterol-rich domains in biological membranes.