Repositioning of transmembrane alpha-helices during membrane protein folding.
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.
Kauko
Anni
A
Center for Biomembrane Research and Stockholm Bioinformatics Center, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
Hedin
Linnea E
LE
Thebaud
Estelle
E
Cristobal
Susana
S
Elofsson
Arne
A
von Heijne
Gunnar
G
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
D027322:Amino Acid Transport System X-AG; D008565:Membrane Proteins