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Upstream charged and hydrophobic residues impact the timing of membrane insertion of transmembrane helices
Author(s) -
Nicolaus Felix,
Ibrahimi Fatima,
Besten Anne,
Heijne Gunnar
Publication year - 2022
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14286
Subject(s) - transmembrane domain , transmembrane protein , chemistry , biophysics , membrane protein , membrane , loop (graph theory) , sequence (biology) , helix (gastropod) , escherichia coli , crystallography , biochemistry , biology , ecology , receptor , mathematics , combinatorics , snail , gene
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.