title: Dynamical features of the Plasmodium falciparum ribosome during translation.
abstract: Plasmodium falciparum, the mosquito-transmitted Apicomplexan parasite, causes the most severe form of human malaria. In the asexual blood-stage, the parasite resides within erythrocytes where it proliferates, multiplies and finally spreads to new erythrocytes. Development of drugs targeting the ribosome, the site of protein synthesis, requires specific knowledge of its structure and work cycle, and, critically, the ways they differ from those in the human host. Here, we present five cryo-electron microscopy (cryo-EM) reconstructions of ribosomes purified from P. falciparum blood-stage schizonts at sub-nanometer resolution. Atomic models were built from these density maps by flexible fitting. Significantly, our study has taken advantage of new capabilities of cryo-EM, in visualizing several structures co-existing in the sample at once, at a resolution sufficient for building atomic models. We have discovered structural and dynamic features that differentiate the ribosomes of P. falciparum from those of mammalian system. Prompted by the absence of RACK1 on the ribosome in our and an earlier study we confirmed that RACK1 does not specifically co-purify with the 80S fraction in schizonts. More extensive studies, using cryo-EM methodology, of translation in the parasite will provide structural knowledge that may lead to development of novel anti-malarials.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Boston, MA 02115, USA Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Blomqvist
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Sanchaita
authors.initials: S
authors.lastname: Das
authors.affiliation: CNRS, Architecture et Réactivité de l'ARN, Université de Strasbourg, Strasbourg 67084, France.
authors.forename: Yaser
authors.initials: Y
authors.lastname: Hashem
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Boston, MA 02115, USA Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA jeffrey.dvorin@childrens.harvard.edu.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Dvorin
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA jf2192@cumc.columbia.edu.
authors.forename: Joachim
authors.identifier: http://orcid.org/0000-0001-5449-6943
authors.initials: J
authors.lastname: Frank
mesh_terms: D020285:Cryoelectron Microscopy; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development; D014176:Protein Biosynthesis; D012335:RNA, Ribosomal / Q000737:chemistry; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000032:analysis; D054682:Ribosome Subunits, Small, Eukaryotic / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry*
chemical_list: D012335:RNA, Ribosomal; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface