Specialized structural and functional roles of residues selectively conserved in subfamilies of the pleckstrin homology domain family

Naveenkumar, Nagarajan and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy (2019) Specialized structural and functional roles of residues selectively conserved in subfamilies of the pleckstrin homology domain family. In: FEBS OPEN BIO, 9 (11). pp. 1848-1859.

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Abstract

Homologous domains embedded in multidomain proteins of different domain architectures (DA) may exhibit subtle, but important, differences in their structure and function. Here, we consider two multidomain proteins, Arf nucleotide binding site opener (ARNO) and G protein-coupled receptor kinase 2 (GRK2), which have very different DAs, but both contain pleckstrin homology (PH) domains. We analyzed the roles of residues selectively conserved in these subfamilies of PH domains from ARNO and GRK2 proteins. DA-specific residues in PH domain are found to contribute to structural and functional specialization of ARNO and GRK2 in terms of (a) specific intra- and interprotein interactions; (b) specificity for phospholipids; and (c) participation in conformational excursions, leading to various functional forms. Our approach can also be applied to subfamilies of other protein families to identify subfamily-specific residues and their specialized roles.

Item Type:	Journal Article
Publication:	FEBS OPEN BIO
Publisher:	WILEY
Additional Information:	Copyright of this article belongs to WILEY
Keywords:	Arf6; ARNO; GRK2; multidomain proteins; PH domain; phosphoinositide binding
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	17 Dec 2019 10:46
Last Modified:	17 Dec 2019 10:46
URI:	http://eprints.iisc.ac.in/id/eprint/63852

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