title: Membrane insertion of marginally hydrophobic transmembrane helices depends on sequence context.
abstract: In mammalian cells, most integral membrane proteins are initially inserted into the endoplasmic reticulum membrane by the so-called Sec61 translocon. However, recent predictions suggest that many transmembrane helices (TMHs) in multispanning membrane proteins are not sufficiently hydrophobic to be recognized as such by the translocon. In this study, we have screened 16 marginally hydrophobic TMHs from membrane proteins of known three-dimensional structure. Indeed, most of these TMHs do not insert efficiently into the endoplasmic reticulum membrane by themselves. To test if loops or TMHs immediately upstream or downstream of a marginally hydrophobic helix might influence the insertion efficiency, insertion of marginally hydrophobic helices was also studied in the presence of their neighboring loops and helices. The results show that flanking loops and nearest-neighbor TMHs are sufficient to ensure the insertion of many marginally hydrophobic helices. However, for at least two of the marginally hydrophobic helices, the local interactions are not enough, indicating that post-insertional rearrangements are involved in the folding of these proteins.
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Linnea E
authors.initials: LE
authors.lastname: Hedin
authors.forename: Karin
authors.initials: K
authors.lastname: Ojemalm
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernsel
authors.forename: Aron
authors.initials: A
authors.lastname: Hennerdal
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Illergård
authors.forename: Karl
authors.initials: K
authors.lastname: Enquist
authors.forename: Anni
authors.initials: A
authors.lastname: Kauko
authors.forename: Susana
authors.initials: S
authors.lastname: Cristobal
authors.forename: Gunnar
authors.initials: G
authors.lastname: von Heijne
authors.forename: Mirjam
authors.initials: M
authors.lastname: Lerch-Bader
authors.forename: IngMarie
authors.initials: I
authors.lastname: Nilsson
authors.forename: Arne
authors.initials: A
authors.lastname: Elofsson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D011506:Proteins