Asn- and Asp-mediated interactions between transmembrane helices during translocon-mediated membrane protein assembly.
Inter-helix hydrogen bonding involving asparagine (Asn, N), glutamine (Gln, Q), aspartic acid (Asp, D) or glutamic acid (Glu, E) can drive efficient di- or trimerization of transmembrane helices in detergent micelles and lipid bilayers. Likewise, Asn-Asn and Asp-Asp pairs can promote the formation of helical hairpins during translocon-mediated membrane protein assembly in the endoplasmic reticulum. By in vitro translation of model integral membrane protein constructs in the presence of rough microsomes, we show that Asn- or Asp-mediated interactions with a neighbouring transmembrane helix can enhance the membrane insertion efficiency of a marginally hydrophobic transmembrane segment. Our observations suggest that inter-helix hydrogen bonds can form during Sec61 translocon-assisted insertion and thus could be important for membrane protein assembly.
Meindl-Beinker
Nadja M
NM
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden.
Lundin
Carolina
C
Nilsson
Ingmarie
I
White
Stephen H
SH
von Heijne
Gunnar
G
D000595:Amino Acid Sequence; D000818:Animals; D001216:Asparagine / Q000737:chemistry*; D001224:Aspartic Acid / Q000737:chemistry*; D019281:Dimerization; D004285:Dogs; D006860:Hydrogen Bonding; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010179:Pancreas / Q000201:enzymology; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000235:genetics; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary
D008565:Membrane Proteins; D001224:Aspartic Acid; D001216:Asparagine; D010447:Peptide Hydrolases