Membrane structure and conformational changes of the antibiotic heterodimeric peptide distinctin by solid-state NMR spectroscopy Export

@article{citeulike:5856327, abstract = {10.1073/pnas.0905069106 The heterodimeric antimicrobial peptide distinctin is composed of 2 linear peptide chains of 22- and 25-aa residues that are connected by a single intermolecular S-S bond. This heterodimer has been considered to be a unique example of a previously unrecorded class of bioactive peptides. Here the 2 distinctin chains were prepared by chemical peptide synthesis in quantitative amounts and labeled with N, as well as N and H, at selected residues, respectively, and the heterodimer was formed by oxidation. CD spectroscopy indicates a high content of helical secondary structures when associated with POPC/POPG 3:1 vesicles or in membrane-mimetic environments. The propensity for helix formation follows the order heterodimer >chain 2 >chain 1, suggesting that peptide-peptide and peptide-lipid interactions both help in stabilizing this secondary structure. In a subsequent step the peptides were reconstituted into oriented phospholipid bilayers and investigated by H and proton-decoupled N solid-state NMR spectroscopy. Whereas chain 2 stably inserts into the membrane at orientations close to perfectly parallel to the membrane surface in the presence or absence of chain 1, the latter adopts a more tilted alignment, which further increases in the heterodimer. The data suggest that membrane interactions result in considerable conformational rearrangements of the heterodimer. Therefore, chain 2 stably anchors the heterodimer in the membrane, whereas chain 1 interacts more loosely with the bilayer. These structural observations are consistent with the antimicrobial activities when the individual chains are compared to the dimer.}, author = {Resende, Jarbas M. and Moraes, Cl\~{A}{\copyright}ria M. and Munhoz, Victor H. O. and Aisenbrey, Christopher and Verly, Rodrigo M. and Bertani, Philippe and Cesar, Amary and Pil\~{A}³-Veloso, Dorila and Bechinger, Burkhard}, citeulike-article-id = {5856327}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0905069106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/39/16639.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/39/16639.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19805350}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19805350}, day = {29}, doi = {10.1073/pnas.0905069106}, journal = {Proceedings of the National Academy of Sciences}, keywords = {antimicrobial, chains, membrane, peptide, resend09pdf, two}, month = {September}, number = {39}, pages = {16639--16644}, posted-at = {2009-09-30 01:05:25}, priority = {2}, title = {Membrane structure and conformational changes of the antibiotic heterodimeric peptide distinctin by solid-state NMR spectroscopy}, url = {http://dx.doi.org/10.1073/pnas.0905069106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:5856327 L3 - citeulike-article-id:5856327 N2 - 10.1073/pnas.0905069106 The heterodimeric antimicrobial peptide distinctin is composed of 2 linear peptide chains of 22- and 25-aa residues that are connected by a single intermolecular S-S bond. This heterodimer has been considered to be a unique example of a previously unrecorded class of bioactive peptides. Here the 2 distinctin chains were prepared by chemical peptide synthesis in quantitative amounts and labeled with N, as well as N and H, at selected residues, respectively, and the heterodimer was formed by oxidation. CD spectroscopy indicates a high content of helical secondary structures when associated with POPC/POPG 3:1 vesicles or in membrane-mimetic environments. The propensity for helix formation follows the order heterodimer >chain 2 >chain 1, suggesting that peptide-peptide and peptide-lipid interactions both help in stabilizing this secondary structure. In a subsequent step the peptides were reconstituted into oriented phospholipid bilayers and investigated by H and proton-decoupled N solid-state NMR spectroscopy. Whereas chain 2 stably inserts into the membrane at orientations close to perfectly parallel to the membrane surface in the presence or absence of chain 1, the latter adopts a more tilted alignment, which further increases in the heterodimer. The data suggest that membrane interactions result in considerable conformational rearrangements of the heterodimer. Therefore, chain 2 stably anchors the heterodimer in the membrane, whereas chain 1 interacts more loosely with the bilayer. These structural observations are consistent with the antimicrobial activities when the individual chains are compared to the dimer. IS - 39 JF - Proceedings of the National Academy of Sciences EP - 16644 TI - Membrane structure and conformational changes of the antibiotic heterodimeric peptide distinctin by solid-state NMR spectroscopy VL - 106 SP - 16639 KW - antimicrobial KW - chains KW - membrane KW - peptide KW - resend09pdf KW - two AU - Resende, Jarbas AU - Moraes, Cléria AU - Munhoz, Victor AU - Aisenbrey, Christopher AU - Verly, Rodrigo AU - Bertani, Philippe AU - Cesar, Amary AU - Piló-Veloso, Dorila AU - Bechinger, Burkhard PY - 2009/09/29/ UR - http://dx.doi.org/10.1073/pnas.0905069106 ER -