title: The lasso segment is required for functional dimerization of the Plasmodium formin 1 FH2 domain.
abstract: Apicomplexan parasites, such as the malaria-causing Plasmodium species, utilize a unique way of locomotion and host cell invasion. This substrate-dependent gliding motility requires rapid cycling of actin between the monomeric state and very short, unbranched filaments. Despite the crucial role of actin polymerization for the survival of the malaria parasite, the majority of Plasmodium cellular actin is present in the monomeric form. Plasmodium lacks most of the canonical actin nucleators, and formins are essentially the only candidates for this function in all Apicomplexa. The malaria parasite has two formins, containing conserved formin homology (FH) 2 and rudimentary FH1 domains. Here, we show that Plasmodium falciparum formin 1 associates with and nucleates both mammalian and Plasmodium actin filaments. Although Plasmodium profilin alone sequesters actin monomers, thus inhibiting polymerization, its monomer-sequestering activity does not compete with the nucleating activity of formin 1 at an equimolar profilin-actin ratio. We have determined solution structures of P. falciparum formin 1 FH2 domain both in the presence and absence of the lasso segment and the FH1 domain, and show that the lasso is required for the assembly of functional dimers.
authors.affiliation: Department of Biochemistry, University of Oulu, Oulu, Finland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ignatev
authors.forename: Saligram Prabhakar
authors.initials: SP
authors.lastname: Bhargav
authors.forename: Juha
authors.initials: J
authors.lastname: Vahokoski
authors.forename: Petri
authors.initials: P
authors.lastname: Kursula
authors.forename: Inari
authors.initials: I
authors.lastname: Kursula
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003001:Cloning, Molecular; D019281:Dimerization; D005326:Fetal Proteins / Q000737:chemistry / Q000378:metabolism*; D000080865:Formins; D008124:Locomotion / Q000502:physiology*; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics* / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D053838:Scattering, Small Angle
chemical_list: D000199:Actins; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins