TY - JOUR
T1 - A naturally occurring peptide with an elementary single disulfide-directed β-hairpin fold
AU - Robinson, Samuel
AU - Chhabra, Sandeep
AU - Belgi, Alessia
AU - Chittoor, Balasubramanyam
AU - Safavi-Hemami, Helena
AU - Robinson, Andrea J
AU - Papenfuss, Anthony T.
AU - Purcell, Anthony
AU - Norton, Raymond
PY - 2016/2/2
Y1 - 2016/2/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84953305680&partnerID=8YFLogxK
U2 - 10.1016/j.str.2015.11.015
DO - 10.1016/j.str.2015.11.015
M3 - Article
AN - SCOPUS:84953305680
VL - 24
SP - 293
EP - 299
JO - Structure
JF - Structure
SN - 0969-2126
IS - 2
ER -