Flanking Residues Help Determine Whether a Hydrophobic Segment Adopts a Monotopic or Bitopic Topology in the Endoplasmic Reticulum Membrane

作者：Norholm Morten H H; Shulga Yulia V; Aoki Satoko; Epand Richard M; von Heijne Gunnar^*

来源：Journal of Biological Chemistry, 2011, 286(28): 25284-25290.

DOI：10.1074/jbc.M111.244616

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.

• 出版日期2011-7-15