title: Repositioning of transmembrane alpha-helices during membrane protein folding.
abstract: We have determined the optimal placement of individual transmembrane helices in the Pyrococcus horikoshii Glt(Ph) glutamate transporter homolog in the membrane. The results are in close agreement with theoretical predictions based on hydrophobicity, but do not, in general, match the known three-dimensional structure, suggesting that transmembrane helices can be repositioned relative to the membrane during folding and oligomerization. Theoretical analysis of a database of membrane protein structures provides additional support for this idea. These observations raise new challenges for the structure prediction of membrane proteins and suggest that the classical two-stage model often used to describe membrane protein folding needs to be modified.
authors.affiliation: Center for Biomembrane Research and Stockholm Bioinformatics Center, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Anni
authors.initials: A
authors.lastname: Kauko
authors.forename: Linnea E
authors.initials: LE
authors.lastname: Hedin
authors.forename: Estelle
authors.initials: E
authors.lastname: Thebaud
authors.forename: Susana
authors.initials: S
authors.lastname: Cristobal
authors.forename: Arne
authors.initials: A
authors.lastname: Elofsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: von Heijne
mesh_terms: D000595:Amino Acid Sequence; D027322:Amino Acid Transport System X-AG / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry*; D006031:Glycosylation; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D043902:Pyrococcus horikoshii / Q000737:chemistry* / Q000166:cytology; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics
chemical_list: D027322:Amino Acid Transport System X-AG; D008565:Membrane Proteins