Both isoforms of mammalian phosphatidylinositol transfer protein are capable of binding and transporting sphingomyelin.
The structurally related mammalian alpha and beta isoforms of phosphatidylinositol (PtdIns) transfer protein (PITP) bind reversibly a single phospholipid molecule, preferably PtdIns or phosphatidylcholine (PtdCho), and transport that lipid between membrane surfaces. PITPbeta, but not PITPalpha, is reported extensively in the scientific literature to exhibit the additional capacity to bind and transport sphingomyelin (CerPCho). We undertook a detailed investigation of the lipid binding and transfer specificity of the soluble mammalian PITP isoforms. We employed a variety of donor and acceptor membrane lipid compositions to determine the sensitivity of recombinant rat PITPalpha and PITPbeta isoforms toward PtdIns, PtdCho, CerPCho, and phosphatidate (PtdOH). Results indicated often striking differences in protein-phospholipid and protein-membrane interactions. We demonstrated unequivocally that both isoforms were capable of binding and transferring CerPCho; we confirmed that the beta isoform was the more active. The order of transfer specific activity was similar for both isoforms: PtdIns>PtdCho>CerPCho>>PtdOH. Independently, we verified the binding of CerPCho to both isoforms by showing an increase in holoprotein isoelectric point following the exchange of protein-bound phosphatidylglycerol for membrane-associated CerPCho. We conclude that PITPalpha and PITPbeta are able to bind and transport glycero- and sphingophospholipids.
Li
Hong
H
Department of Biochemistry and Molecular Biology, School of Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City 66160-7421, USA.
Tremblay
Jacqueline M
JM
Yarbrough
Lynwood R
LR
Helmkamp
George M
GM
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D007526:Isoelectric Point; D008565:Membrane Proteins; D015394:Molecular Structure; D010715:Phosphatidylglycerols / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*
D002352:Carrier Proteins; D008565:Membrane Proteins; D010715:Phosphatidylglycerols; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; D013109:Sphingomyelins