Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain
Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain
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DOI：
10.1093/emboj/16.18.5501
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发表时间：
1997-09-15
期刊：
影响因子：
11.4
通讯作者：
Simons, K
中科院分区：
文献类型：
--
作者：
Scheiffele, P;Roth, MG;Simons, K
鞘磷脂-胆固醇筏是生物膜上的微区，具有液态相的性质，与膜的交通和信号事件有关。我们以流感病毒血凝素(HA)为模型蛋白，分析了跨膜蛋白与这些微区的相互作用。在这里，我们证明了RAFT关联是蛋白质中编码的一种内在属性。带有外源跨膜区(TMD)序列的突变HA分子失去了与脂质微区结合的能力，并且HA TMD的突变揭示了与膜的外质叶接触需要疏水残基。我们还提供了实验证据，证明胆固醇是蛋白质与脂筏结合所必需的。我们的数据表明，与特定膜结构域的结合可以在跨膜蛋白中编码，这一信息将用于极化分类和信号转导过程。
Sphingolipid-cholesterol rafts are microdomains in biological membranes with liquid-ordered phase properties which are implicated in membrane traffic and signalling events, We have used influenza virus haemagglutinin (HA) as a model protein to analyse the interaction of transmembrane proteins with these microdomains. Here we demonstrate that raft association is an intrinsic property encoded in the protein. Mutant HA molecules with foreign transmembrane domain (TMD) sequences lose their ability to associate with the lipid microdomains, and mutations in the HA TMD reveal a requirement for hydrophobic residues in contact with the exoplasmic leaflet of the membrane. We also provide experimental evidence that cholesterol is critically required for association of proteins with lipid rafts. Our data suggest that the binding to specific membrane domains can be encoded in transmembrane proteins and that this information will be used for polarized sorting and signal transduction processes.