Reversible transition between alpha-helix and beta-sheet conformation of a transmembrane domain.
Despite the important functions of protein transmembrane domains, their structure and dynamics are often scarcely known. The SNARE proteins VAMP/synaptobrevin and syntaxin 1 are implicated in membrane fusion. Using different spectroscopic approaches we observed a marked sensitivity of their transmembrane domain structure in regard to the lipid/peptide ratio. In the dilute condition, peptides corresponding to the complete transmembrane domain fold into an alpha-helix inserted at approximately 35 degrees to the normal of the membranes, an observation in line with molecular simulations. Upon an increase in the peptide/lipid ratio, the peptides readily exhibited transition to beta-sheet structure. Moreover, the insertion angle of these beta-sheets increased to 54 degrees and was accompanied by a derangement of lipid acyl chains. For both proteins the transition from alpha-helix to beta-sheet was reversible under certain conditions by increasing the peptide/lipid ratio. This phenomenon was observed in different model systems including multibilayers and small unilamellar vesicles. In addition, differences in peptide structure and transitions were observed when using distinct lipids (DMPC, DPPC or DOPC) thus indicating parameters influencing transmembrane domain structure and conversion from helices to sheets. The putative functional consequences of this unprecedented dynamic behavior of a transmembrane domain are discussed.
Yassine
Wissam
W
Université de Bordeaux, UMR CNRS 5248 Chemistry and Biology of Membranes and Nano-Objects, Institut Européen de Chimie et Biologie, 2, rue Robert Escarpit, F-33607 PESSAC, France.
Taib
Nada
N
Federman
Silvina
S
Milochau
Alexandra
A
Castano
Sabine
S
Sbi
Walid
W
Manigand
Claude
C
Laguerre
Michel
M
Desbat
Bernard
B
Oda
Reiko
R
Lang
Jochen
J
D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D050827:Syntaxin 1 / Q000737:chemistry*; D053835:Unilamellar Liposomes / Q000737:chemistry; D050987:Vesicle-Associated Membrane Protein 1 / Q000737:chemistry*
D008051:Lipid Bilayers; D050827:Syntaxin 1; D053835:Unilamellar Liposomes; D050987:Vesicle-Associated Membrane Protein 1; D004134:Dimyristoylphosphatidylcholine