Influence of hydrophobic mismatch and palmitoylation on the association of transmembrane alpha-helical peptides with detergent-resistant membranes.
The aim of this study was to gain insight into the mechanism through which transmembrane proteins are targeted to liquid ordered (L(o)) phase domains or rafts. This was investigated by analyzing the Triton X-100 resistance of designed transmembrane peptides in model membranes of 1,2-dioleoyl-sn-glycero-3-phosphocholine, sphingomyelin and cholesterol (1/1/1, molar ratio), which contain both L(o) phase domains and fluid bilayers. By using peptides with one or two palmitate chains covalently linked to their N-terminus or with variable hydrophobic lengths, the roles of protein palmitoylation and of mismatch between the transmembrane segment of the protein and the bilayer thickness, respectively, were investigated. The results show that neither hydrophobic matching nor palmitoylation is sufficient for partitioning of peptides into L(o) phase domains. It is concluded that the L(o) phase itself, due to the tight packing of the lipids, constitutes an unfavorable environment for accommodation of protein transmembrane segments.
Department of Biochemistry of Membranes, CBLE, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands. b.y.vanduyl@chem.uu.nl
Bianca Y
BY
van Duyl
Dirk T S
DT
Rijkers
Ben
B
de Kruijff
J Antoinette
JA
Killian
D001665:Binding Sites; D002784:Cholesterol / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects* / Q000378:metabolism; D008567:Membranes, Artificial; D017830:Octoxynol / Q000737:chemistry / Q000494:pharmacology*; D010168:Palmitates / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D017433:Protein Structure, Secondary; D013109:Sphingomyelins / Q000737:chemistry
D008563:Membrane Lipids; D008565:Membrane Proteins; D008567:Membranes, Artificial; D010168:Palmitates; D010455:Peptides; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D017830:Octoxynol; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine