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Designed Peptides (designed + peptide)
Selected AbstractsRotational orientation of monomers within a designed homo-oligomer transmembrane helical bundlePROTEIN SCIENCE, Issue 4 2005Kathleen P. Howard Abstract A peptide designed to form a homo-oligomeric transmembrane helical bundle was reconstituted into lipid bilayers and studied by using 2H NMR (nuclear magnetic resonance) with magic angle spinning to confirm that the helical interface corresponds to the interface intended in the design. The peptide belongs to a family of model peptides derived from a membrane-solubilized version of the water-soluble coiled-coil GCN4-P1. The variant studied here contains two asparagines thought to engage in interhelical hydrogen bonding critical to the formation of a stable trimer. For the NMR studies, three different peptides were synthesized, each with one of three consecutive leucines in the transmembrane region deuterium labeled. Prior to NMR data collection, polarized infrared spectroscopy was used to establish that the peptides were reconstituted in lipid bilayers in a transmembrane helical conformation. The 2H NMR line shapes of the three different peptides are consistent with a trimer structure formed by the designed peptide that is stabilized by inter-helical hydrogen bonding of asparagines at positions 7 and 14. [source] ,-Hairpin folding and stability: molecular dynamics simulations of designed peptides in aqueous solutionJOURNAL OF PEPTIDE SCIENCE, Issue 9 2004Clara M. Santiveri Abstract The structural properties of a 10-residue and a 15-residue peptide in aqueous solution were investigated by molecular dynamics simulation. The two designed peptides, SYINSDGTWT and SESYINSDGTWTVTE, had been studied previously by NMR at 278 K and the resulting model structures were classified as 3:5 ,-hairpins with a type I + G1 ,-bulge turn. In simulations at 278 K, starting from the NMR model structure, the 3:5 ,-hairpin conformers proved to be stable over the time period evaluated (30 ns). Starting from an extended conformation, simulations of the decapeptide at 278 K, 323 K and 353 K were also performed to study folding. Over the relatively short time scales explored (30 ns at 278 K and 323 K, 56 ns at 353 K), folding to the 3:5 ,-hairpin could only be observed at 353 K. At this temperature, the collapse to ,-hairpin-like conformations is very fast. The conformational space accessible to the peptide is entirely dominated by loop structures with different degrees of ,-hairpin character. The transitions between different types of ordered loops and ,-hairpins occur through two unstructured loop conformations stabilized by a single side-chain interaction between Tyr2 and Trp9, which facilitates the changes of the hydrogen-bond register. In agreement with previous experimental results, ,-hairpin formation is initially driven by the bending propensity of the turn segment. Nevertheless, the fine organization of the turn region appears to be a late event in the folding process. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Synthetic peptides mimicking the interleukin-6/gp 130 interaction: a two-helix bundle system.JOURNAL OF PEPTIDE SCIENCE, Issue 2 2003Design, conformational studies Abstract The objective of our study was to mimic in a typical reductionist approach the molecular interactions observed at the interface between the gp 130 receptor and interleukin-6 during formation of their complex. A peptide system obtained by reproducing some of the interleukin-6/gp 130 molecular interactions into a two-helix bundle structure was investigated. The solution conformational features of this system were determined by CD and NMR techniques. The CD titration experiments demonstrated that the interaction between the designed peptides is specific and based on a well-defined stoichiometry. The NMR data confirmed some of the structural features of the binding mechanism as predicted by the rational design and indicated that under our conditions the recognition specificity and affinity can be explained by the formation of a two-helix bundle. Thus, the data reported herein represent a promising indication on how to develop new peptides able to interfere with formation of the interleukin-6/gp 130 complex. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd. [source] | ||||||||||