Interaction of peptides spanning the transmembrane domain of caveolin-1 with model membranes

Caveolin-1 has an atypical membrane-spanning domain comprising of 34 residues. Caveolin-1 targets to lipid droplets under certain conditions, where they are involved in signaling and cholesterol balance. In the present study, membrane association of synthetic peptides corresponding to the membrane-spanning domain of caveolin-1 has been investigated to obtain an insight into the topology of transmembrane region in the lipid bilayer and the effect of truncations in this sequence, as observed in the targeting to lipid droplets, by using model membranes. Fluorescence studies revealed strong association of the peptide corresponding to the membrane-spanning domain of caveolin-1 with anionic lipids as compared with zwitterionic lipids, which is consistent with the location of this domain in the cytoplasmic side of the plasma membrane. Association of a short 9 residue peptide corresponding to the C-terminus of caveolin-1 membrane-spanning domain with lipid vesicles revealed the importance of this region for association with model membranes. Our investigations indicate that the peptide corresponding to the membrane-spanning domain of caveolin-1 does not span the lipid bilayer. We propose that both caveolin scaffolding domain and transmembrane segment of caveolin-1 contribute to the strong association with the plasma membrane rendering the protein highly detergent resistant.