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Mapping the chemical and sequence space of the ShKT superfamily

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dc.contributor.authorShafee, T.
dc.contributor.authorMitchell, M.L.
dc.contributor.authorNorton, R.S.
dc.date.issued2019
dc.description.abstractThe ShKT superfamily is widely distributed throughout nature and encompasses a wide range of documented functions and processes, from modulation of potassium channels to involvement in morphogenesis pathways. Cysteine-rich secretory proteins (CRISPs) contain a cysteine-rich domain (CRD) at the C-terminus that is similar in structure to the ShK fold. Despite the structural similarity of the CRD and ShK-like domains, we know little of the sequence-function relationships in these families. Here, for the first time, we examine the evolution of the biophysical properties of sequences within the ShKT superfamily in relation to function, with a focus on the ShK-like superfamily. ShKT data were sourced from published sequences in the protein family database, in addition to new ShK-like sequences from the Australian speckled anemone (Oulactis sp.). Our analysis clearly delineates the ShK-like family from the CRDs of CRISP proteins. The four CRISP subclusters separate out into the main phyla of Mammalia, Insecta and Reptilia. The ShK-like family is in turn composed of seven subclusters, the largest of which contains members from across the eukaryotes, with a continuum of intermediate properties. Smaller sub-clusters contain specialised members such as nematode ShK-like sequences. Several of these ShKT sub-clusters contain no functionally characterised sequences. This chemical space analysis should be useful as a guide to select sequences for functional studies and to gain insight into the evolution of these highly divergent sequences with an ancient conserved fold.
dc.description.statementofresponsibilityThomas Shafee, Michela L. Mitchell, Raymond S. Norton
dc.identifier.citationToxicon, 2019; 165:95-102
dc.identifier.doi10.1016/j.toxicon.2019.04.008
dc.identifier.issn0041-0101
dc.identifier.issn0041-0101
dc.identifier.orcidMitchell, M.L. [0000-0001-6331-534X]
dc.identifier.urihttps://hdl.handle.net/2440/140766
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/arc/LP150100621
dc.relation.grantNHMRC
dc.rights© 2019 Elsevier Ltd. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.toxicon.2019.04.008
dc.subjectShKT; Cysteine-rich peptide; Disulfide-rich protein; Peptide evolution; Peptide structure; Sequence analysis
dc.subject.meshCnidarian Venoms
dc.subject.meshCluster Analysis
dc.subject.meshSequence Analysis, Protein
dc.subject.meshEvolution, Molecular
dc.subject.meshPrincipal Component Analysis
dc.subject.meshModels, Molecular
dc.subject.meshProtein Domains
dc.titleMapping the chemical and sequence space of the ShKT superfamily
dc.typeJournal article
pubs.publication-statusPublished

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