Mapping the chemical and sequence space of the ShKT superfamily

Thomas Shafee, Michela L. Mitchell, Raymond S. Norton

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The 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.

Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalToxicon
Volume165
DOIs
Publication statusPublished - 1 Jul 2019

Keywords

  • Cysteine-rich peptide
  • Disulfide-rich protein
  • Peptide evolution
  • Peptide structure
  • Sequence analysis
  • ShKT

Cite this

Shafee, Thomas ; Mitchell, Michela L. ; Norton, Raymond S. / Mapping the chemical and sequence space of the ShKT superfamily. In: Toxicon. 2019 ; Vol. 165. pp. 95-102.
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Mapping the chemical and sequence space of the ShKT superfamily. / Shafee, Thomas; Mitchell, Michela L.; Norton, Raymond S.

In: Toxicon, Vol. 165, 01.07.2019, p. 95-102.

Research output: Contribution to journalArticleResearchpeer-review

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