Recognition of transmembrane helices by the endoplasmic reticulum translocon.
Membrane proteins depend on complex translocation machineries for insertion into target membranes. Although it has long been known that an abundance of nonpolar residues in transmembrane helices is the principal criterion for membrane insertion, the specific sequence-coding for transmembrane helices has not been identified. By challenging the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments, we have determined the basic features of this code, including a 'biological' hydrophobicity scale. We find that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Our results indicate that direct protein-lipid interactions are critical during translocon-mediated membrane insertion.
Hessa
Tara
T
Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
Kim
Hyun
H
Bihlmaier
Karl
K
Lundin
Carolina
C
Boekel
Jorrit
J
Andersson
Helena
H
Nilsson
Ingmarie
I
White
Stephen H
SH
von Heijne
Gunnar
G
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D021381:Protein Transport; D000069816:SEC Translocation Channels; D055672:Static Electricity; D013816:Thermodynamics
D000596:Amino Acids; D008565:Membrane Proteins; D010446:Peptide Fragments; D000069816:SEC Translocation Channels