Pleckstrin homology (PH)-like domains in bacteria (PHb)
Pleckstrin homology (PH) domains were first identified in eukaryotic proteins. Recently PH-like domains have been identified in bacteria as well. These PHb form dome-shaped oligomeric rings with a conserved hydrophilic surface at the intersection of the beta-strands of adjacent protomers that likely mediates protein-protein interactions. It is now thought that the PH domain superfamily is more widespread than previous thought and appears to have existed before prokaryotes and eukaryotes diverged. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.
Jiyao W et al.(2023). "The conserved domain database in 2023.",