title: Disulfide bonds versus TrpTrp pairs in irregular beta-hairpins: NMR structure of vammin loop 3-derived peptides as a case study.
abstract: Structural studies on model peptides have led to a good understanding of the rules behind the formation and stability of regular beta-hairpins. To test their applicability to the successful design of irregular beta-hairpins with long loops and/or beta-bulges at the strands, we mimicked loop 3 of vammin, a 4:6 beta-hairpin with a non-Gly beta-bulge. The most stabilising cross-strand pairs, disulfide bonds or/and TrpTrp pairs, were incorporated at non-hydrogen-bonded sites in peptides spanning the 69-80 region of vammin. According to NMR data, these modified peptides adopt beta-hairpin conformations as intended by design. The Trp-containing peptides reproduce even the unusual positive phi angle for the Gln residue, with the indole rings in the preferred edge-to-face orientation. For the first time the beta-hairpin-stabilising capacities of a disulfide bond and a TrpTrp pair are compared in the same model system. We found that the contribution to stability of the noncovalent indole-indole interaction is larger than that of the covalent disulfide bond, and that their combination gives rise to an even more stable beta-hairpin.
authors.affiliation: Instituto de Química Física Rocasolano, CSIC, Serrano 119, 28006 Madrid, Spain.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Mirassou
authors.forename: Clara M
authors.initials: CM
authors.lastname: Santiveri
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Pérez de Vega
authors.forename: Rosario
authors.initials: R
authors.lastname: González-Muñiz
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Jiménez
mesh_terms: D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D014364:Tryptophan / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry*; D014757:Viper Venoms / Q000737:chemistry*
chemical_list: D004220:Disulfides; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D014757:Viper Venoms; C519402:vammin protein, Vipera ammodytes ammodytes; D014364:Tryptophan