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

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

Research output: Contribution to journal › Journal article › Research › peer-review

15 Citations (Scopus)

29 Downloads (Pure)

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.

Original language	English
Journal	Structure
Volume	24
Issue number	2
Pages (from-to)	293-299
Number of pages	7
ISSN	0969-2126
DOIs	https://doi.org/10.1016/j.str.2015.11.015
Publication status	Published - 2016
Externally published	Yes

Keywords

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

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10.1016/j.str.2015.11.015

A Naturally Occurring Peptide with an Elementary Single Disulfide-Directed β-Hairpin FoldFinal published version, 1.4 MB

Cite this

A Naturally Occurring Peptide with an Elementary Single Disulfide-Directed β-Hairpin Fold. / Robinson, Samuel D; Chhabra, Sandeep; Belgi, Alessia; Chittoor, Balasubramanyam; Safavi-Hemami, Helena; Robinson, Andrea J; Papenfuss, Anthony T; Purcell, Anthony W; Norton, Raymond S.

In: Structure, Vol. 24, No. 2, 2016, p. 293-299.

Research output: Contribution to journal › Journal article › Research › peer-review

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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. ",

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AU - Robinson, Samuel D

AU - Chhabra, Sandeep

AU - Belgi, Alessia

AU - Chittoor, Balasubramanyam

AU - Safavi-Hemami, Helena

AU - Robinson, Andrea J

AU - Papenfuss, Anthony T

AU - Purcell, Anthony W

AU - Norton, Raymond S

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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.

KW - Animals

KW - Cysteine

KW - Mass Spectrometry

KW - Models, Molecular

KW - Mollusk Venoms/chemistry

KW - Neuropeptides/chemistry

KW - Peptides/chemistry

KW - Protein Folding

KW - Protein Structure, Secondary

KW - Snails/chemistry

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