Disulfide bonds versus TrpTrp pairs in irregular beta-hairpins: NMR structure of vammin loop 3-derived peptides as a case study

• Published in: Chembiochem : a European journal of chemical biology Vol. 10; no. 5; p. 902
• Main Authors: Mirassou, Yasmina, Santiveri, Clara M, Pérez de Vega, M Jesús, González-Muñiz, Rosario, Jiménez, M Angeles
• Format: Journal Article
• Language: English
• Published: Germany 23-03-2009
• Subjects: Amino Acid Sequence; Disulfides - chemistry; Molecular Sequence Data; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Peptides - chemistry; Protein Folding; Protein Structure, Secondary; Sequence Alignment; Tryptophan - chemistry; Vascular Endothelial Growth Factor A - chemistry; Viper Venoms - chemistry
• ISSN: 1439-7633
• DOI: 10.1002/cbic.200800834

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.