| Literature References | 1. GOLDSCHMIDT-CLERMONT, P.J. AND JAMMEY, P.A.
Profilin, a weak CAP for actin and RAS.
CELL 66 419-421 (1991).
2. THERIOT, J.A. AND MITCHISON, T.J.
The three faces of profilin.
CELL 75 835-838 (1993).
3. METZIER, W.J., FARMER, B.T., CONSTANTINE, K.L., FRIEDRICHS, M.S.,
LAVOLE, T. AND MUELLER, L.
Refined solution structure of human profilin I.
PROTEIN SCI. 4 450-459 (1995).
4. ASTURIAS, J.A., ARILLA, M.C., GOMEZ-BAYON, N., MARTINEZ, A. AND
PALACIOS, R.
Recombinant DNA technology in allergology: cloning and expression of plant
profilins.
ALLERGOL.IMMUNOPATHOL. 25 127-134 (1997).
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| Documentation | Profilin is a ubiquitous eukaryotic protein that plays an active role in
the regulation of actin polymerisation. In view of its relatively small
molecular mass (12-15kDa), the functions of profilin are complex and
diverse. Under some circumstances, the protein sequesters actin monomers
and inhibits filament growth; under others, it "desequesters" actin monomers
and actively promotes filament growth. Desequestering involves binding of
profilin to the fast-growing ends of actin-filaments, which accelerates the
exchange of the adenine nucleotide bound to monomeric actin. ATP-actin
monomers polymerise faster than ADP-actin, and make stiffer filaments.
Therefore, under conditions of rapid filament reorganisation, where large
amounts of ADP-actin monomers are produced, and in the presence of a large
excess of ATP over ADP, profilin may actually promote polymerisation [1,2].
Profilin is probably also involved in some signalling pathways. It has been
shown to bind tightly and specifically to phosphoinositides (PIP). Its
binding to PIP2 in lipid bilayers protects PIP2 from hydrolysis by soluble
phosphoinositol-specific phospholipase C. Interestingly, the activity of RAS
is controlled by mitogenically active phospholipids. Two proteins that
regulate the GTPase activity of H-Ras (GAP and GIP) are regulated in
opposite ways by specific phospholipids, including polyphosphoinositides and
diacylglycerol. The net result of the phospholipid regulation of these two
proteins is the activation of H-Ras. This suggests that profilin may
participate in the pathway activated by receptor tyrosine kinases and may
be part of the mechanism by which receptor tyrosine kinases control the
reorganisation of the cytoskeleton. Thus, the regulation of profilin may
be an important link between growth factor signals from the outside world
and the internal state of the actin cytoskeleton [1,2].
Profilin homologues are present in organisms ranging from fungi and amoebae,
to trees and mammals; a protein structurally similar to profilin is also
present in the genome of variola and vaccinia viruses. Profilin is, in part,
responsible for cross-reactivities in pollen and food allergic patients.
Although the N-terminal region of profilins, which is thought to be involved
in actin binding, is relatively well conserved, in general, sequence
similarities between profilins from different species is low. The
differences are especially pronounced between mammal-specific and all
other profilins.
The structure of profilin has been determined by NMR [3]. The protein folds
into a single compact globular domain, which is bisected by an extended
anti-parallel beta-sheet. Two alpha-helices (which include the N- and
C-terminal residues) lie on the convex face of the sheet, and 3 smaller
helices lie on the concave face [3,4].
PROFILINPLNT is a 7-element fingerprint that provides a signature for plant
profilins. The fingerprint was derived from an initial alignment of 10
sequences: the motifs were drawn from conserved regions spanning the full
alignment length, focusing on those sections that characterise the
plant profilins but distinguish them from the rest of the profilin
family - motif 1 encodes alpha-helix 1; motif 2 spans strand 2; motif 3
spans the C-terminus of helix 2 and the loop preceding strand 3; motif 4
spans strand 4 and the following loop; motif 5 encodes strands 5 and 6;
motif 6 spans the C-terminus of strand 7 and the N-terminus of helix 3; and
motif 7 encodes the C-terminus of helix 3. Three iterations on SPTR39_17f
were required to reach convergence, at which point a true set comprising 55
sequences was identified. Eight partial matches were also found, all of
which are non-plant profilins that match motifs 1, 2, 5 and/or 7.
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