7C4C

The crystal structure of Trypanosoma brucei RNase D : GMP complex

Summary for 7C4C

• Entry DOI: 10.2210/pdb7c4c/pdb
• Descriptor: CCHC-type domain-containing protein, ZINC ION, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: trypanosoma brucei, rnase d, guide rna degradation, rna binding protein, gmp
• Biological source: Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
• Total number of polymer chains: 1
• Total formula weight: 41160.98

Authors

Gao, Y.Q.,Gan, J.H. (deposition date: 2020-05-15, release date: 2021-04-07, Last modification date: 2024-10-16)

Primary citation

Gao, Y.,Liu, H.,Zhang, C.,Su, S.,Chen, Y.,Chen, X.,Li, Y.,Shao, Z.,Zhang, Y.,Shao, Q.,Li, J.,Huang, Z.,Ma, J.,Gan, J.
Structural basis for guide RNA trimming by RNase D ribonuclease in Trypanosoma brucei.
Nucleic Acids Res., 49:568-583, 2021

PubMed Abstract: Infection with kinetoplastid parasites, including Trypanosoma brucei (T. brucei), Trypanosoma cruzi (T. cruzi) and Leishmania can cause serious disease in humans. Like other kinetoplastid species, mRNAs of these disease-causing parasites must undergo posttranscriptional editing in order to be functional. mRNA editing is directed by gRNAs, a large group of small RNAs. Similar to mRNAs, gRNAs are also precisely regulated. In T. brucei, overexpression of RNase D ribonuclease (TbRND) leads to substantial reduction in the total gRNA population and subsequent inhibition of mRNA editing. However, the mechanisms regulating gRNA binding and cleavage by TbRND are not well defined. Here, we report a thorough structural study of TbRND. Besides Apo- and NMP-bound structures, we also solved one TbRND structure in complexed with single-stranded RNA. In combination with mutagenesis and in vitro cleavage assays, our structures indicated that TbRND follows the conserved two-cation-assisted mechanism in catalysis. TbRND is a unique RND member, as it contains a ZFD domain at its C-terminus. In addition to T. brucei, our studies also advanced our understanding on the potential gRNA degradation pathway in T. cruzi, Leishmania, as well for as other disease-associated parasites expressing ZFD-containing RNDs.

PubMed: 33332555
DOI: 10.1093/nar/gkaa1197

Experimental method

X-RAY DIFFRACTION (2.265 Å)