Inter-helical hydrogen bond formation during membrane protein integration into the ER membrane.
Recent work has shown that efficient di- or trimerization of hydrophobic transmembrane helices in detergent micelles or lipid bilayers can be driven by inter-helix hydrogen bonding involving polar residues such as Asn or Asp. Using in vitro translation in the presence of rough microsomes of a model integral membrane protein, we now show that the formation of so-called helical hairpins, two tightly spaced transmembrane helices connected by a short loop, can likewise be promoted by the introduction of Asn-Asn or Asp-Asp pairs in a long transmembrane hydrophobic segment. These observations suggest that inter-helix hydrogen bonds can form within the context of the Sec61 translocon in the endoplasmic reticulum, implying that hydrophobic segments in a nascent polypeptide chain in transit through the Sec61 channel have immediate access to a non-aqueous subcompartment within the translocon.
Hermansson
Marika
M
Department of Biochemistry and Biophysics, Stockholm University, SE-106 91, Stockholm, Sweden.
von Heijne
Gunnar
G
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006860:Hydrogen Bonding; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D008565:Membrane Proteins; D012697:Serine Endopeptidases; C026515:type I signal peptidase