Flanking residues help determine whether a hydrophobic segment adopts a monotopic or bitopic topology in the endoplasmic reticulum membrane.

Nørholm MH, Shulga YV, Aoki S, Epand RM, von Heijne G

J. Biol. Chem. 286 (28) 25284-25290 [2011-07-15; online 2011-05-23]

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 ε isoform of human diacylglycerol kinase (DGKε), 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 DGKε 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.

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PubMed 21606504

DOI 10.1074/jbc.M111.244616

Crossref 10.1074/jbc.M111.244616

M111.244616

pmc PMC3137099