Structural and dynamic properties of juxta-membrane segments of caveolin-1 and caveolin-2 at the membrane interface Export

@article{citeulike:6008056, abstract = {Abstract\ \ Caveolins (cav1–3) are essential membrane proteins found in caveolae. The caveolin scaffolding domain of cav-1 includes a short sequence containing a CRAC motif (V94TKYWFYR101) at its C-terminal end. To investigate the role of this motif in the caveolin–membrane interaction at the atomic level, we performed a detailed structural and dynamics characterization of a cav-1(V94-L102) nonapeptide encompassing this motif and including the first residue of cav-1 hydrophobic domain (L102), in dodecylmaltoside (DM) or dodecylphosphocholine (DPC) micelles, as membrane mimics. Cav-1(V94-L102) partitioned better in DPC and in DM/anionic lipid micelles than in DM micelles, as shown by fluorescence titration and CD. NMR data revealed that this peptide folded as an amphipathic helix located in the polar head group region of DPC micelles. The two tyrosine side-chains, flanked by arginine and lysine residues, are situated on one face of this helix, whereas the phenylalanine and tryptophan side-chains are located on the opposite face. Fluorescence studies showed significant Trp subnanosecond rotations, the presence of several rotamers, and a heterogeneous location within the water/micelle interface. NMR studies of the shorter cav-1(V94-R101) peptide and of the homologous sequence of cav-2(I79SKYVMYKF87) allowed the description of the effect of L102 and of the amino acid variations occurring in cav-2 on the structure and localization in DPC micelles. Based on the topological model of caveolins, our results suggest that the cav-1 and cav-2 nonapeptides studied form interfacial α-helix membrane anchors in which the K/RhhhYK/Rh motif, also found in cav-3, may play a significant role.}, author = {Le Lan, Charlotte and Gallay, Jacques and Vincent, Michel and Neumann, Jean and de Foresta, B\'{e}atrice and Jamin, Nad\`{e}ge}, citeulike-article-id = {6008056}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00249-009-0548-4}, citeulike-linkout-1 = {http://www.springerlink.com/content/r801038377572k1q}, doi = {10.1007/s00249-009-0548-4}, journal = {European Biophysics Journal}, keywords = {caveolin, dynmics, fluorescence, interaction, lan09pdf, membrane}, posted-at = {2009-10-26 00:53:33}, priority = {2}, title = {Structural and dynamic properties of juxta-membrane segments of caveolin-1 and caveolin-2 at the membrane interface}, url = {http://dx.doi.org/10.1007/s00249-009-0548-4} }

TY - JOUR ID - citeulike:6008056 L3 - citeulike-article-id:6008056 N2 - Abstract  Caveolins (cav1–3) are essential membrane proteins found in caveolae. The caveolin scaffolding domain of cav-1 includes a short sequence containing a CRAC motif (V94TKYWFYR101) at its C-terminal end. To investigate the role of this motif in the caveolin–membrane interaction at the atomic level, we performed a detailed structural and dynamics characterization of a cav-1(V94-L102) nonapeptide encompassing this motif and including the first residue of cav-1 hydrophobic domain (L102), in dodecylmaltoside (DM) or dodecylphosphocholine (DPC) micelles, as membrane mimics. Cav-1(V94-L102) partitioned better in DPC and in DM/anionic lipid micelles than in DM micelles, as shown by fluorescence titration and CD. NMR data revealed that this peptide folded as an amphipathic helix located in the polar head group region of DPC micelles. The two tyrosine side-chains, flanked by arginine and lysine residues, are situated on one face of this helix, whereas the phenylalanine and tryptophan side-chains are located on the opposite face. Fluorescence studies showed significant Trp subnanosecond rotations, the presence of several rotamers, and a heterogeneous location within the water/micelle interface. NMR studies of the shorter cav-1(V94-R101) peptide and of the homologous sequence of cav-2(I79SKYVMYKF87) allowed the description of the effect of L102 and of the amino acid variations occurring in cav-2 on the structure and localization in DPC micelles. Based on the topological model of caveolins, our results suggest that the cav-1 and cav-2 nonapeptides studied form interfacial α-helix membrane anchors in which the K/RhhhYK/Rh motif, also found in cav-3, may play a significant role. JF - European Biophysics Journal TI - Structural and dynamic properties of juxta-membrane segments of caveolin-1 and caveolin-2 at the membrane interface KW - caveolin KW - dynmics KW - fluorescence KW - interaction KW - lan09pdf KW - membrane AU - Le Lan, Charlotte AU - Gallay, Jacques AU - Vincent, Michel AU - Neumann, Jean AU - de Foresta, Béatrice AU - Jamin, Nadège UR - http://dx.doi.org/10.1007/s00249-009-0548-4 ER -