Mapping the chemical and sequence space of the ShKT superfamily

Shafee, Thomas, Mitchell, Michela L., and Norton, Raymond S. (2019) Mapping the chemical and sequence space of the ShKT superfamily. Toxicon, 165. pp. 95-102.

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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.

Item ID: 82704
Item Type: Article (Research - C1)
ISSN: 0041-0101
Keywords: Cysteine-rich peptide, Disulfide-rich protein, Peptide evolution, Peptide structure, Sequence analysis, ShKT
Copyright Information: © 2019 Elsevier Ltd. All rights reserved.
Funders: Australian Research Council (ARC)
Projects and Grants: ARC linkage grant LP150100621
Date Deposited: 14 May 2024 00:59
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320506 Medical biochemistry - proteins and peptides (incl. medical proteomics) @ 50%
31 BIOLOGICAL SCIENCES > 3105 Genetics > 310510 Molecular evolution @ 25%
31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310299 Bioinformatics and computational biology not elsewhere classified @ 25%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 50%
28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 50%
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