title: Large tilts in transmembrane helices can be induced during tertiary structure formation.
abstract: While early structural models of helix-bundle integral membrane proteins posited that the transmembrane α-helices [transmembrane helices (TMHs)] were orientated more or less perpendicular to the membrane plane, there is now ample evidence from high-resolution structures that many TMHs have significant tilt angles relative to the membrane. Here, we address the question whether the tilt is an intrinsic property of the TMH in question or if it is imparted on the TMH during folding of the protein. Using a glycosylation mapping technique, we show that four highly tilted helices found in multi-spanning membrane proteins all have much shorter membrane-embedded segments when inserted by themselves into the membrane than seen in the high-resolution structures. This suggests that tilting can be induced by tertiary packing interactions within the protein, subsequent to the initial membrane-insertion step.
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, SE-17177 Solna, Sweden.
authors.forename: Minttu
authors.initials: M
authors.lastname: Virkki
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden.
authors.forename: Carolina
authors.initials: C
authors.lastname: Boekel
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, SE-17177 Solna, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Illergård
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, SE-17177 Solna, Sweden.
authors.forename: Christoph
authors.initials: C
authors.lastname: Peters
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, SE-17177 Solna, Sweden.
authors.forename: Nanjiang
authors.initials: N
authors.lastname: Shu
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, SE-17177 Solna, Sweden.
authors.forename: Konstantinos D
authors.initials: KD
authors.lastname: Tsirigos
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, SE-17177 Solna, Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Elofsson
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden; Science for Life Laboratory, Stockholm University, SE-17177 Solna, Sweden. Electronic address: gunnar@dbb.su.se.
authors.forename: Gunnar
authors.initials: G
authors.lastname: von Heijne
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden. Electronic address: ingmarie@dbb.su.se.
authors.forename: IngMarie
authors.initials: I
authors.lastname: Nilsson
mesh_terms: D000595:Amino Acid Sequence; D030562:Databases, Protein; D006031:Glycosylation; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D008565:Membrane Proteins
keywords: membrane protein folding; translocon; transmembrane helix