La Trobe
Mapping the chemical and sequence space of the ShKT (postprint).pdf (1.6 MB)
Download file

Mapping the chemical and sequence space of the ShKT superfamily

Download (1.6 MB)
journal contribution
posted on 06.01.2021, 05:40 by Thomas ShafeeThomas Shafee, Michela L Mitchell, Raymond S Norton
© 2019 Elsevier Ltd

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.

Funding

The authors acknowledge Dr. Rodrigo A. V. Morales and Edward Airey for their contribution to the preparation of sequences used in the analysis. This project was funded in part by ARC linkage grant LP150100621. M.L.M acknowledges an Australian Government Research Training Program Scholarship, Monash Medicinal Chemistry Faculty Scholarship and Monash University - Museum Victoria Scholarship top-up. R.S.N acknowledges fellowship support from the Australian National Health and Medical Research Council.

ARC | LP150100621

Australian Government Research Training Program Scholarship

Monash Medicinal Chemistry Faculty Scholarship

Australian National Health and Medical Research Council

Monash University - Museum Victoria Scholarship

History

Publication Date

01/07/2019

Journal

Toxicon

Volume

165

Pagination

8p. (p. 95-102)

Publisher

Elsevier

ISSN

0041-0101

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.