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bioRxiv · 10.1101/2021.12.23.474019

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

Nicolaus, F.·Ibrahimi, F.·den Besten, A.·von Heijne, G.
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Abstract

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 center. 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 BtuC protein: 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.

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Nicolaus, F., Ibrahimi, F., den Besten, A., von Heijne, G.. 2021-12-24. Upstream charged and hydrophobic residues impact the timing of membrane insertion of transmembrane helices. https://doi.org/10.1101/2021.12.23.474019

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