PDBsum entry 2jkf

Protein binding

PDB id: 2jkf

Contents

Protein chain

170 a.a. *

Waters ×83

* Residue conservation analysis

PDB id:

2jkf

Name:

Protein binding

Title:

Plasmodium falciparum profilin

Structure:

Profilin. Chain: a. Synonym: conserved protein. Engineered: yes

Source:

Plasmodium falciparum. Organism_taxid: 5833. Expressed in: escherichia coli. Expression_system_taxid: 469008. Other_details: codonplusripl

Resolution:

2.31Å R-factor: 0.204 R-free: 0.269

Authors:

I.Kursula,P.Kursula,M.Ganter,S.Panjikar,K.Matuschewski,H.Schueler

Key ref:

I.Kursula et al. (2008). Structural Basis for Parasite-Specific Functions of the Divergent Profilin of Plasmodium falciparum. Structure, 16, 1638-1648. PubMed id: 19000816 DOI: 10.1016/j.str.2008.09.008

Date:

28-Aug-08 Release date: 23-Sep-08

Protein chain

P86294  (PROF_PLAFX) -  Profilin from Plasmodium falciparum (isolate HB3)

Seq: 171 a.a.

Struc: 170 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.str.2008.09.008

Structure 16:1638-1648 (2008)

PubMed id: 19000816

Structural Basis for Parasite-Specific Functions of the Divergent Profilin of Plasmodium falciparum.

I.Kursula, P.Kursula, M.Ganter, S.Panjikar, K.Matuschewski, H.Schüler.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from Cell Press: Structure (2008, 16, 1638-1648) copyright 2008.

Figures were selected by an automated process.