5OGW

Cryo-EM structure of jasplakinolide-stabilized malaria parasite F-actin at near-atomic resolution

Summary for 5OGW

• Entry DOI: 10.2210/pdb5ogw/pdb
• EMDB information: 3805
• Descriptor: Actin-1, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: f-actin, plasmodium, malaria parasite, cytoskeleton, cryo-em, jas, jasplakinolide, filament, glideosome, gliding motility, thin filament, structural protein
• Biological source: Plasmodium falciparum (isolate HB3)
• Total number of polymer chains: 5
• Total formula weight: 214624.92

Authors

Pospich, S.,Kumpula, E.-P.,von der Ecken, J.,Vahokoski, J.,Kursula, I.,Raunser, S. (deposition date: 2017-07-13, release date: 2017-09-27, Last modification date: 2024-07-10)

Primary citation

Pospich, S.,Kumpula, E.P.,von der Ecken, J.,Vahokoski, J.,Kursula, I.,Raunser, S.
Near-atomic structure of jasplakinolide-stabilized malaria parasite F-actin reveals the structural basis of filament instability.
Proc. Natl. Acad. Sci. U.S.A., 114:10636-10641, 2017

PubMed Abstract: During their life cycle, apicomplexan parasites, such as the malaria parasite , use actomyosin-driven gliding motility to move and invade host cells. For this process, actin filament length and stability are temporally and spatially controlled. In contrast to canonical actin, actin 1 (Act1) does not readily polymerize into long, stable filaments. The structural basis of filament instability, which plays a pivotal role in host cell invasion, and thus infectivity, is poorly understood, largely because high-resolution structures of Act1 filaments were missing. Here, we report the near-atomic structure of jasplakinolide (JAS)-stabilized Act1 filaments determined by electron cryomicroscopy. The general filament architecture is similar to that of mammalian F-actin. The high resolution of the structure allowed us to identify small but important differences at inter- and intrastrand contact sites, explaining the inherent instability of apicomplexan actin filaments. JAS binds at regular intervals inside the filament to three adjacent actin subunits, reinforcing filament stability by hydrophobic interactions. Our study reveals the high-resolution structure of a small molecule bound to F-actin, highlighting the potential of electron cryomicroscopy for structure-based drug design. Furthermore, our work serves as a strong foundation for understanding the structural design and evolution of actin filaments and their function in motility and host cell invasion of apicomplexan parasites.

PubMed: 28923924
DOI: 10.1073/pnas.1707506114

Experimental method

ELECTRON MICROSCOPY (3.8 Å)