5J4B

Crystal structure of the Thermus thermophilus 70S ribosome in complex with cisplatin (co-crystallized) and bound to mRNA and A-, P- and E-site tRNAs at 2.6A resolution

This is a non-PDB format compatible entry.

Summary for 5J4B

• Entry DOI: 10.2210/pdb5j4b/pdb
• Related: 5J4C
• Descriptor: 23S ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total)
• Functional Keywords: ribosome, cisplatin, anticancer drug, cytotoxicity, inhibition of translation, translocation, mrna channel, gtpase activating center
• Biological source: Escherichia coli; More
• Total number of polymer chains: 112
• Total formula weight: 4580570.97

Authors

Melnikov, S.V.,Soll, D.,Steitz, T.A.,Polikanov, Y.S. (deposition date: 2016-03-31, release date: 2016-04-27, Last modification date: 2023-11-15)

Primary citation

Melnikov, S.V.,Soll, D.,Steitz, T.A.,Polikanov, Y.S.
Insights into RNA binding by the anticancer drug cisplatin from the crystal structure of cisplatin-modified ribosome.
Nucleic Acids Res., 44:4978-4987, 2016

PubMed Abstract: Cisplatin is a widely prescribed anticancer drug, which triggers cell death by covalent binding to a broad range of biological molecules. Among cisplatin targets, cellular RNAs remain the most poorly characterized molecules. Although cisplatin was shown to inactivate essential RNAs, including ribosomal, spliceosomal and telomeric RNAs, cisplatin binding sites in most RNA molecules are unknown, and therefore it remains challenging to study how modifications of RNA by cisplatin contributes to its toxicity. Here we report a 2.6Å-resolution X-ray structure of cisplatin-modified 70S ribosome, which describes cisplatin binding to the ribosome and provides the first nearly atomic model of cisplatin-RNA complex. We observe nine cisplatin molecules bound to the ribosome and reveal consensus structural features of the cisplatin-binding sites. Two of the cisplatin molecules modify conserved functional centers of the ribosome-the mRNA-channel and the GTPase center. In the mRNA-channel, cisplatin intercalates between the ribosome and the messenger RNA, suggesting that the observed inhibition of protein synthesis by cisplatin is caused by impaired mRNA-translocation. Our structure provides an insight into RNA targeting and inhibition by cisplatin, which can help predict cisplatin-binding sites in other cellular RNAs and design studies to elucidate a link between RNA modifications by cisplatin and cisplatin toxicity.

PubMed: 27079977
DOI: 10.1093/nar/gkw246

Experimental method

X-RAY DIFFRACTION (2.6 Å)