Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins.

ABSTRACT: Pleckstrin homology (PH) domains are presumed to bind phosphoinositides (PIPs), but specific interaction with and regulation by PIPs for most PH domain-containing proteins are unclear. Here we employ a single-molecule pulldown assay to study interactions of lipid vesicles with full-length proteins in mammalian whole cell lysates. Of 67 human PH domain-containing proteins initially examined, 36 (54%) are found to have affinity for PIPs with various specificity, the majority of which have not been reported before. Further investigation of ARHGEF3 reveals distinct structural requirements for its binding to PI(4,5)P₂ and PI(3,5)P₂, and functional relevance of its PI(4,5)P₂ binding. We generate a recursive-learning algorithm based on the assay results to analyze

SUBMITTER: Singh N 

PROVIDER: S-EPMC8282632 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature