PDBsum entry 4cbu

Motor protein

PDB id: 4cbu

Contents

Protein chains

357 a.a.

125 a.a.

Ligands

ATP

Metals

_CA ×3

Waters ×819

PDB id:

4cbu

Name:

Motor protein

Title:

Crystal structure of plasmodium falciparum actin i

Structure:

Actin-1. Chain: a. Synonym: pfact1,actin i,pfacti. Engineered: yes. Gelsolin. Chain: g. Fragment: residues 50-174. Synonym: actin-depolymerizing factor,adf,brevin. Engineered: yes

Source:

Plasmodium falciparum. Malaria parasite p. Falciparum. Organism_taxid: 5833. Gene: act1, acti, pf3d7_1246200, pfl2215w. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Mus musculus. House mouse. Organism_taxid: 10090.

Resolution:

1.30Å R-factor: 0.122 R-free: 0.153

Authors:

J.Vahokoski,S.P.Bhargav,A.Desfosses,M.Andreadaki,E.P.Kumpula, A.Ignatev,S.Munico Martinez,S.Lepper,F.Frischknecht,I.Siden-Kiamos, C.Sachse,I.Kursula

Key ref:

J.Vahokoski et al. (2014). Structural differences explain diverse functions of Plasmodium actins. Plos Pathog, 10, e1004091. PubMed id: 24743229 DOI: 10.1371/journal.ppat.1004091

Date:

16-Oct-13 Release date: 30-Apr-14

Protein chain

Q8I4X0  (ACT1_PLAF7) -  Actin-1 from Plasmodium falciparum (isolate 3D7)

Seq: 376 a.a.

Struc: 357 a.a.

Protein chain

P13020  (GELS_MOUSE) -  Gelsolin from Mus musculus

Seq: 780 a.a.

Struc: 125 a.a.

Enzyme reactions

• Enzyme class 1: Chain A: E.C.3.6.4.- - ?????
• Enzyme class 2: Chain G: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1371/journal.ppat.1004091

Plos Pathog 10:e1004091 (2014)

PubMed id: 24743229

Structural differences explain diverse functions of Plasmodium actins.

J.Vahokoski, S.P.Bhargav, A.Desfosses, M.Andreadaki, E.P.Kumpula, S.M.Martinez, A.Ignatev, S.Lepper, F.Frischknecht, I.Sidén-Kiamos, C.Sachse, I.Kursula.

ABSTRACT

Actins are highly conserved proteins and key players in central processes in all eukaryotic cells. The two actins of the malaria parasite are among the most divergent eukaryotic actins and also differ from each other more than isoforms in any other species. Microfilaments have not been directly observed in Plasmodium and are presumed to be short and highly dynamic. We show that actin I cannot complement actin II in male gametogenesis, suggesting critical structural differences. Cryo-EM reveals that Plasmodium actin I has a unique filament structure, whereas actin II filaments resemble canonical F-actin. Both Plasmodium actins hydrolyze ATP more efficiently than α-actin, and unlike any other actin, both parasite actins rapidly form short oligomers induced by ADP. Crystal structures of both isoforms pinpoint several structural changes in the monomers causing the unique polymerization properties. Inserting the canonical D-loop to Plasmodium actin I leads to the formation of long filaments in vitro. In vivo, this chimera restores gametogenesis in parasites lacking actin II, suggesting that stable filaments are required for exflagellation. Together, these data underline the divergence of eukaryotic actins and demonstrate how structural differences in the monomers translate into filaments with different properties, implying that even eukaryotic actins have faced different evolutionary pressures and followed different paths for developing their polymerization properties.