Phosphatidylinositol
transfer proteins are highly conserved, soluble eukaryotic proteins
that
binds reversibly one molecule of phosphatidylinositol (PtdIns),
phosphatidylcholine
(PtdCho), or sphingomyelin (CerPCho).
An in vitro activity of transferring the
structurally
diverse glycerophospholipids PtdIns and PtdCho between a variety of
membranes was described over
30 years ago (University of Utrecht, Utrecht NL) and served as a
means of quantitating "catalytic" activity
and monitoring purification of proteins from bovine brain and liver.
Typically, the rate at which a "tagged"
phospholipid
(radiolabelled, fluorescent, spin-labeled) moves through the aqueous
phase from a
donor membrane to an acceptor membrane is markedly enhanced in the
presence of PtdIns transfer proteins These proteins are, therefore,
capable
of extracting phospholipids from and inserting them into a membrane
surface. Evidence from the laboratories of Shamshad Cockcroft
(University College, London UK) and Thomas Martin (University of
Wisconsin)
supports the participation of PtdIns transfer proteins in signal
transduction
processes that proceed through the phosphorylation and hydrolysis of
phosphoinositides.
In the past few years my laboratory has been investigating
structure-function
relationships of the recombinant rat and human PtdIns transfer protein
isoforms PITPα
and PITPβ. Much of my current
research is being performed in collaboration with the laboratories of
Lynwood
Yarbrough (University of Kansas Medical Center) and Marilyn Yoder
(University of Missouri - Kansas City). Our physical
characterization studies
are being carried out on recombinant and crystallized PtdIns transfer
protein
isoforms
and a variety of structural mutants.
Several
cellular functions have
been
described...
Altered
protein
levels suggests essential role in cell viability...
Phospholipid
is required for correct protein folding...
Free
and membrane-bound protein have different conformations...
The
specificity of lipid binding and transfer is being elucidated...
An
interactive tour of the structure of PITPα complexed with PtdCho...
