Open AccessSpecialized structural and functional roles of residues selectively conserved in subfamilies of the pleckstrin homology domain family
Author(s) -
Naveenkumar Nagarajan,
Sowdhamini Ramanathan,
Srinivasan Narayanaswamy
Publication year - 2019
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12725
Subject(s) - pleckstrin homology domain , homology (biology) , sequence homology , homology modeling , domain (mathematical analysis) , computational biology , conserved sequence , biology , genetics , biochemistry , base sequence , gene , signal transduction , enzyme , mathematical analysis , mathematics
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.