Flanking Residues Help Determine Whether a Hydrophobic Segment Adopts a Monotopic or Bitopic Topology in the Endoplasmic Reticulum Membrane
Flanking Residues Help Determine Whether a Hydrophobic Segment Adopts a Monotopic or Bitopic Topology in the Endoplasmic Reticulum Membrane
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DOI：
10.1074/jbc.m111.244616
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发表时间：
2011-07-15
影响因子：
4.8
通讯作者：
von Heijne, Gunnar
中科院分区：
文献类型：
--
作者：
Norholm, Morten H. H.;Shulga, Yulia V.;von Heijne, Gunnar
通过单个疏水片段与膜相互作用的蛋白质可分为单位或双位。在这里，我们探讨了膜附着酶（人二酰基甘油激酶的 epsilon 异构体（DGK epsilon））插入粗糙微粒体时的拓扑结构，并将其与单位膜蛋白小鼠 Caveolin-1 进行比较。与之前的发现相反，DGK epsilon 中的 N 端疏水延伸在我们的实验系统中实现了双位拓扑而不是单位拓扑。此外，我们发现带电荷的侧翼残基以及嵌入疏水片段中的脯氨酸残基是单位与双位拓扑的重要决定因素。
Proteins interacting with membranes via a single hydrophobic segment can be classified as either monotopic or bitopic. Here, we probe the topology of a membrane-attached enzyme, the epsilon isoform of human diacylglycerol kinase (DGK epsilon), when inserted into rough microsomes and compare it with the monotopic membrane protein mouse caveolin-1. In contrast to previous findings, the N-terminal hydrophobic stretch in DGK epsilon attains a bitopic rather than a monotopic topology in our experimental system. In addition, we find that charged flanking residues as well as proline residues embedded in the hydrophobic segment are important determinants of monotopic versus bitopic topology.