A Naturally Occurring Peptide with an Elementary Single Disulfide-Directed β-Hairpin Fold

Samuel D Robinson; Sandeep Chhabra; Alessia Belgi; Balasubramanyam Chittoor; Helena Safavi-Hemami; Andrea J Robinson; Anthony T Papenfuss; Anthony W Purcell; Raymond S Norton

doi:10.1016/j.str.2015.11.015

A Naturally Occurring Peptide with an Elementary Single Disulfide-Directed β-Hairpin Fold

Structure. 2016 Feb 2;24(2):293-9. doi: 10.1016/j.str.2015.11.015. Epub 2016 Jan 7.

Authors

Samuel D Robinson¹, Sandeep Chhabra¹, Alessia Belgi², Balasubramanyam Chittoor¹, Helena Safavi-Hemami³, Andrea J Robinson², Anthony T Papenfuss⁴, Anthony W Purcell⁵, Raymond S Norton⁶

Affiliations

¹ Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
² School of Chemistry, Monash University, Clayton, VIC 3800, Australia.
³ Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
⁴ Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
⁵ The Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia.
⁶ Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia. Electronic address: ray.norton@monash.edu.

PMID: 26774129
DOI: 10.1016/j.str.2015.11.015

Abstract

Certain peptide folds, owing to a combination of intrinsic stability and resilience to amino acid substitutions, are particularly effective for the display of diverse functional groups. Such "privileged scaffolds" are valuable as starting points for the engineering of new bioactive molecules. We have identified a precursor peptide expressed in the venom gland of the marine snail Conus victoriae, which appears to belong to a hitherto undescribed class of molluscan neuropeptides. Mass spectrometry matching with the venom confirmed the complete mature peptide sequence as a 31-residue peptide with a single disulfide bond. Solution structure determination revealed a unique peptide fold that we have designated the single disulfide-directed β hairpin (SDH). The SDH fold is highly resistant to thermal denaturation and forms the core of several other multiple disulfide-containing peptide folds, including the inhibitor cystine knot. This elementary fold may offer a valuable starting point for the design and engineering of new bioactive peptides.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cysteine
Mass Spectrometry
Models, Molecular
Mollusk Venoms / chemistry*
Neuropeptides / chemistry*
Peptides / chemistry*
Protein Folding
Protein Structure, Secondary
Snails / chemistry*

Substances

Mollusk Venoms
Neuropeptides
Peptides
Cysteine