Upstream charged and hydrophobic residues impact the timing of membrane insertion of transmembrane helices.

JSON

Nicolaus F, Ibrahimi F, den Besten A, von Heijne G

FEBS Lett. 596 (8) 1004-1012 [2022-04-00; online 2022-01-31]

During SecYEG-mediated cotranslational insertion of membrane proteins, transmembrane helices (TMHs) first make contact with the membrane when their N-terminal end is ~ 45 residues away from the peptidyl transferase centre. However, we recently uncovered instances where the first contact is delayed by up to ~ 10 residues. Here, we recapitulate these effects using a model TMH fused to two short segments from the Escherichia coli inner membrane protein BtuC: a positively charged loop and a re-entrant loop. We show that the critical residues are two Arg residues in the positively charged loop and four hydrophobic residues in the re-entrant loop. Thus, both electrostatic and hydrophobic interactions involving sequence elements that are not part of a TMH can impact the way the latter behaves during membrane insertion.

PubMed 35038773

DOI 10.1002/1873-3468.14286

Crossref 10.1002/1873-3468.14286