Key result
Molecular dynamics simulation captures the TbREL1 pre-ligation state to reveal RNA binding specificity.
Why the study?
The functional dynamics and catalytic mechanism of RNA ligation by kinetoplastid RNA-editing ligases are not fully understood.
This molecular dynamics simulation provides insights into the functional dynamics and catalytic mechanism of RNA ligation by TbREL1 in Trypanosoma brucei.
Members of the genus Trypanosoma, which include the pathogenic species Trypanosoma brucei and Trypanosoma cruzi, edit their post-transcriptional mitochondrial RNA via a multiprotein complex called the editosome. In T. brucei, the RNA is nicked prior to uridylate insertion and deletion. Following editing, nicked RNA is religated by one of two RNA-editing ligases (TbREL). This study describes a recent 70 ns molecular dynamics simulation of TbREL1, an ATP-dependent RNA-editing ligase of the nucleotidyltransferase superfamily that is required for the survival of T. brucei insect and bloodstream forms. In this work, a model of TbREL1 in complex with its full double-stranded RNA (dsRNA) substrate is created on the basis of the homologous relation between TbREL1 and T4 Rnl2. The simulation captures TbREL1 dynamics in the state immediately preceding RNA ligation, providing insights into the functional dynamics and catalytic mechanism of the kinetoplastid ligation reaction. Important features of RNA binding and specificity are revealed for kinetoplastid ligases and the broader nucleotidyltransferase superfamily.
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Swift et al. (2009) studied this question. Molecular dynamics simulation was evaluated on TbREL1 dynamics in the state immediately preceding RNA ligation. A 70 ns molecular dynamics simulation of TbREL1 captured the state immediately preceding RNA ligation, revealing features of RNA binding and specificity for kinetoplastid ligases.
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