Dynamical features of the Plasmodium falciparum ribosome during translation.

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Sun M, Li W, Blomqvist K, Das S, Hashem Y, Dvorin JD, Frank J

Dynamical features of the Plasmodium falciparum ribosome during translation.

Nucleic Acids Res. 2015 Dec 2;43(21):10515-24. doi: 10.1093/nar/gkv991. Epub 2015 Oct 1.

PubMed ID
26432834 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
40S ribosomal protein S3Q8IKH8Details
60S ribosomal protein L4Q8I431Details
60S ribosomal protein L3Q8IJC6Details
40S ribosomal protein S19C0H5C2Details
60S ribosomal protein L2Q8I3T9Details
60S ribosomal protein L27Q8IKM5Details
40S ribosomal protein S5, putativeQ8IBN5Details
40S ribosomal protein S21Q8IHS5Details
60S ribosomal protein L24, putativeQ8IEM3Details
60S ribosomal protein L23Q8IE82Details
60S ribosomal protein L17, putativeQ8IDI5Details
60S ribosomal protein L10, putativeQ8ILV2Details
Ubiquitin-60S ribosomal protein L40Q8ID50Details
60S ribosomal protein L30e, putativeQ8IJK8Details
60S ribosomal protein L21Q8ILK3Details
60S ribosomal protein L14, putativeQ8ILE8Details