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PDBsum entry 2jkf
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Protein binding
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PDB id
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2jkf
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References listed in PDB file
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Key reference
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Title
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Structural basis for parasite-Specific functions of the divergent profilin of plasmodium falciparum.
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Authors
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I.Kursula,
P.Kursula,
M.Ganter,
S.Panjikar,
K.Matuschewski,
H.Schüler.
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Ref.
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Structure, 2008,
16,
1638-1648.
[DOI no: ]
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PubMed id
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Abstract
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Profilins are key regulators of actin dynamics. They sequester actin monomers,
forming a pool for rapid polymer formation stimulated by proteins such as
formins. Apicomplexan parasites utilize a highly specialized microfilament
system for motility and host cell invasion. Their genomes encode only a small
number of divergent actin regulators. We present the first crystal structure of
an apicomplexan profilin, that of the malaria parasite Plasmodium falciparum,
alone and in complex with a polyproline ligand peptide. The most striking
feature of Plasmodium profilin is a unique minidomain consisting of a large
beta-hairpin extension common to all apicomplexan parasites, and an acidic loop
specific for Plasmodium species. Reverse genetics in the rodent malaria model,
Plasmodium berghei, suggests that profilin is essential for the invasive blood
stages of the parasite. Together, our data establish the structural basis for
understanding the functions of profilin in the malaria parasite.
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Figure 4.
Figure 4. Structure of the Plasmodium falciparum Profilin
Bound to an Octaproline Peptide
(A) Overview of the
structure with the peptide. The N- and C-terminal helices (α1
and α4, respectively) are labeled.
(B) Structure of the
polyproline-binding site. The side chains of the 4 aromatic
residues forming the binding site are shown. The C-terminal
α-helix (α4) does not participate in binding interactions as
in mammalian and yeast profilins; instead, the N terminus turns
back toward the peptide (in orange), allowing the
Plasmodium-specific Tyr5 to engage in an intimate interaction
with the peptide (Figure S3). The two direct hydrogen bonds
between the peptide and side chains of Tyr5 and Trp7 are shown
as dashed lines. The N and C termini of the octaproline peptide
are indicated. The electron density shown is the final refined
2F[o]–F[c] map contoured at 1 σ.
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Figure 5.
Figure 5. Overview of the Putative Actin-Binding Site
(A) Surface model of the complex of Plasmodium profilin (green)
with actin (gray). Note the unique β-hairpin domain reaching
upward toward actin on the right. The proline-rich peptide is
shown in orange.
(B–D) Details of the three most
important sites contributing to the profilin-actin interaction,
as discussed in the text. Human profilin 1 and actin (Ferron et
al., 2007) are shown in pink and gray, respectively. The
Plasmodium profilin crystal structure superimposed with the
human profilin 1 from the complex is shown in green.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2008,
16,
1638-1648)
copyright 2008.
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