5ogw

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

spinqualitylabelsall models 5ogw, resolution 3.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ogw is a 5 chain structure with sequence from Plafx. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 9UE, ADP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ACT1_PLAFX] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. Actin assembles into short polymer microfilaments, these are thought to contribute to parasite gliding motility. Publication Abstract from PubMed During their life cycle, apicomplexan parasites, such as the malaria parasite Plasmodium falciparum, 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, P. falciparum actin 1 (PfAct1) 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 PfAct1 filaments were missing. Here, we report the near-atomic structure of jasplakinolide (JAS)-stabilized PfAct1 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. Near-atomic structure of jasplakinolide-stabilized malaria parasite F-actin reveals the structural basis of filament instability.,Pospich S, Kumpula EP, von der Ecken J, Vahokoski J, Kursula I, Raunser S Proc Natl Acad Sci U S A. 2017 Sep 18. pii: 201707506. doi:, 10.1073/pnas.1707506114. PMID:28923924 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Actin

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