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dc.contributor.authorSun, Ming
dc.contributor.authorLi, Wen
dc.contributor.authorBlomqvist, Karin
dc.contributor.authorDas, Sanchaita
dc.contributor.authorHashem, Yaser
dc.contributor.authorDvorin, Jeffrey D.
dc.contributor.authorFrank, Joachim
dc.date2022-08-11T08:09:43.000
dc.date.accessioned2022-08-23T16:41:02Z
dc.date.available2022-08-23T16:41:02Z
dc.date.issued2015-12-02
dc.date.submitted2015-10-29
dc.identifier.citationNucleic Acids Res. 2015 Dec 2;43(21):10515-24. doi: 10.1093/nar/gkv991. Epub 2015 Oct 1. <a href="http://dx.doi.org/10.1093/nar/gkv991">Link to article on publisher's site</a>
dc.identifier.issn0305-1048 (Linking)
dc.identifier.doi10.1093/nar/gkv991
dc.identifier.pmid26432834
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39802
dc.description.abstractPlasmodium 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26432834&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsCopyright The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<a href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</a>), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact <a href="mailto:journals.permissions@oup.com">journals.permissions@oup.com</a>
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectBiophysics
dc.subjectMolecular Biology
dc.subjectParasitic Diseases
dc.subjectParasitology
dc.subjectStructural Biology
dc.titleDynamical features of the Plasmodium falciparum ribosome during translation
dc.typeJournal Article
dc.source.journaltitleNucleic acids research
dc.source.volume43
dc.source.issue21
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3603&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2599
dc.identifier.contextkey7779456
refterms.dateFOA2022-08-23T16:41:02Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/2599
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages10515-24


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Copyright The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<a href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</a>), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact <a href="mailto:journals.permissions@oup.com">journals.permissions@oup.com</a>
Except where otherwise noted, this item's license is described as Copyright The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<a href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</a>), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact <a href="mailto:journals.permissions@oup.com">journals.permissions@oup.com</a>