Membrane-mediated dimerization potentiates PIP5K lipid kinase activity.

ABSTRACT: The phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family of lipid-modifying enzymes generate the majority of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] lipids found at the plasma membrane in eukaryotic cells. PI(4,5)P₂ lipids serve a critical role in regulating receptor activation, ion channel gating, endocytosis, and actin nucleation. Here, we describe how PIP5K activity is regulated by cooperative binding to PI(4,5)P₂ lipids and membrane-mediated dimerization of the kinase domain. In contrast to constitutively dimeric phosphatidylinositol 5-phosphate 4-kinase (PIP4K, type II PIPK), solution PIP5K exists in a weak monomer-dimer equilibrium. PIP5K monomers can associate with PI(4,5)P₂-containing membranes and dimerize in a protein dens

SUBMITTER: Hansen SD 

PROVIDER: S-EPMC9470164 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature