Lipid-binding SRPBCC domain of Class I and Class II Phosphatidylinositol Transfer Proteins
This family includes the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain of the phosphatidylinositol transfer protein (PITP) family of lipid transfer proteins. This family of proteins includes Class 1 PITPs (PITPNA/PITPalpha and PITPNB/PITPbeta, Drosophila vibrator and related proteins), Class IIA PITPs (PITPNM1/PITPalphaI/Nir2, PITPNM2/PITPalphaII/Nir3, Drosophila RdgB, and related proteins), and Class IIB PITPs (PITPNC1/RdgBbeta and related proteins). The PITP family belongs to the SRPBCC domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. In vitro, PITPs bind phosphatidylinositol (PtdIns), as well as phosphatidylcholine (PtdCho) but with a lower affinity. They transfer these lipids from one membrane compartment to another. The cellular roles of PITPs include inositol lipid signaling, PtdIns metabolism, and membrane trafficking. Class III PITPs, exemplified by the Sec14p family, are found in yeast and plants but are unrelated in sequence and structure to Class I and II PITPs and belong to a different superfamily.
Feature 1:lipid binding site [chemical binding site]
Evidence:
Comment:This phospholipid binding site is comprised of a lipid-headgroup binding pocket and two hydrophobic channels which accommodate the acyl chains.
Comment:There are subtle differences in the orientation of PtdCho acyl chains, when this lipid is bound to the different PTIP isoforms.
Structure:1UW5_A; human PITPNA bound with PtdIns, contacts at 4A
Jiyao W et al.(2023). "The conserved domain database in 2023.",