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

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 funct

SUBMITTER: Naveenkumar N 

PROVIDER: S-EPMC6823287 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature