Epand Richard M, Sayer Brian G, Epand Raquel F
Department of Biochemistry, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Biochemistry. 2003 Dec 16;42(49):14677-89. doi: 10.1021/bi035587j.
The peptide N-acetyl-LWYIK-amide causes the reorganization of bilayers of phosphatidylcholine and cholesterol to produce domains enriched in cholesterol. At a cholesterol mol fraction of 0.5, addition of N-acetyl-LWYIK-amide results in the formation of cholesterol crystallites. Addition of this peptide to mixtures of 1-stearoyl-2-oleoylphosphatidylcholine with lower mol fractions of cholesterol results in an increase in the enthalpy of the chain melting transition of the phospholipid, indicating the depletion of cholesterol from a domain in the membrane. The peptide binds to membranes both with and without cholesterol. However, (1)H magic-angle spinning (MAS) nuclear Overhauser effect spectroscopy (NOESY) indicates that in the presence of cholesterol the peptide has greater penetration into the bilayer. (13)C MAS NMR indicates that the peptide has stronger interactions with the A ring of cholesterol than it does with the interior of the bilayer. These results are in contrast with those of another peptide, N-acetyl-KYWFYR-amide, which does not promote the formation of cholesterol crystallites and does not show preferential interaction with cholesterol by NMR. Therefore, cholesterol can promote the insertion of N-acetyl-LWYIK-amide into a membrane and this peptide will sequester cholesterol into domains. These properties help to explain the observation that this sequence is found to be important in causing the fusion protein of human immunodeficiency virus (HIV) to sequester into raft domains in biological membranes.
肽N-乙酰-LWYIK-酰胺可导致磷脂酰胆碱和胆固醇双层结构重排，形成富含胆固醇的结构域。在胆固醇摩尔分数为0.5时，添加N-乙酰-LWYIK-酰胺会导致胆固醇微晶的形成。将此肽添加到胆固醇摩尔分数较低的1-硬脂酰-2-油酰磷脂酰胆碱混合物中，会导致磷脂链熔化转变焓增加，表明膜中一个结构域的胆固醇减少。该肽在有胆固醇和无胆固醇的情况下均能与膜结合。然而，（1）H魔角旋转（MAS）核Overhauser效应光谱（NOESY）表明，在有胆固醇存在时，该肽对双层的穿透性更强。（13）C MAS NMR表明，该肽与胆固醇的A环相互作用比与双层内部的相互作用更强。这些结果与另一种肽N-乙酰-KYWFYR-酰胺的结果相反，后者不会促进胆固醇微晶的形成，且NMR显示其与胆固醇无优先相互作用。因此，胆固醇可促进N-乙酰-LWYIK-酰胺插入膜中，且该肽会将胆固醇隔离到结构域中。这些特性有助于解释以下观察结果：该序列在导致人类免疫缺陷病毒（HIV）融合蛋白隔离到生物膜中的脂筏结构域方面很重要。
