2A1L

Rat PITP-Beta Complexed to Phosphatidylcholine

2A1L の概要

• エントリーDOI: 10.2210/pdb2a1l/pdb
• 分子名称: Phosphatidylinositol transfer protein beta isoform, 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE (3 entities in total)
• 機能のキーワード: lipid binding protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Cytoplasm : P53812
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32151.93

構造登録者

Vordtriede, P.B.,Doan, C.N.,Tremblay, J.M.,Helmkamp, G.M.,Yoder, M.D. (登録日: 2005-06-20, 公開日: 2005-11-29, 最終更新日: 2023-08-23)

主引用文献

Vordtriede, P.B.,Doan, C.N.,Tremblay, J.M.,Helmkamp, G.M.,Yoder, M.D.
Structure of PITPbeta in Complex with Phosphatidylcholine: Comparison of Structure and Lipid Transfer to Other PITP Isoforms.
Biochemistry, 44:14760-14771, 2005

PubMed Abstract: Phosphatidylinositol transfer protein (PITP) is a ubiquitous eukaryotic protein that preferentially binds either phosphatidylinositol or phosphatidylcholine and catalyzes the exchange of these lipids between membranes. Mammalian cytosolic PITPs include the ubiquitously expressed PITPalpha and PITPbeta isoforms (269-270 residues). The crystal structure of rat PITPbeta complexed to dioleoylphosphatidylcholine was determined to 2.18 A resolution with molecular replacement using rat PITPalpha (77% sequence identify) as the phasing model. A structure comparison of the alpha and beta isoforms reveals minimal differences in protein conformation, differences in acyl conformation in the two isoforms, and remarkable conservation of solvent structure around the bound lipid. A comparison of transfer activity by human and rat PITPs, using small unilamellar vesicles with carefully controlled phospholipid composition, indicates that the beta isoforms have minimal differences in transfer preference between PtdIns and PtdCho when donor vesicles contain predominantly PtdCho. When PtdCho and PtdIns are present in equivalent concentrations in donor vesicles, PtdIns transfer occurs at approximately 3-fold the rate of PtdCho. The rat PITPbeta isoform clearly has the most diminished transfer rate of the four proteins studied. With the two rat isoforms, site-directed mutations of two locations within the lipid binding cavity that possess differing biochemical properties were characterized: I84alpha/F83beta and F225alpha/L224beta. The 225/224 locus is more critical in determining substrate specificity. Following the mutation of this locus to the other amino acid, the PtdCho transfer specific activity became PITPalpha (F225L) approximately PITPbeta and PITPbeta (L224F) approximately PITPalpha. The 225alpha/224beta locus plays a modest role in the specificity of both isoforms toward CerPCho.

PubMed: 16274224
DOI: 10.1021/bi051191r

実験手法

X-RAY DIFFRACTION (2.18 Å)