5crk
From Proteopedia
Crystal Structure of the MTERF1 F243A substitution bound to the termination sequence.
Structural highlights
FunctionMTEF1_HUMAN Transcription termination factor. Binds to a 28 bp region within the tRNA(Leu(uur)) gene at a position immediately adjacent to and downstream of the 16S rRNA gene; this region comprises a tridecamer sequence critical for directing accurate termination. Binds DNA along the major grove and promotes DNA bending and partial unwinding. Promotes base flipping. Transcription termination activity appears to be polarized with highest specificity for transcripts initiated on the light strand.[1] Publication Abstract from PubMedHuman mitochondrial transcription termination occurs within the leu-tRNA gene and is mediated by the DNA binding protein MTERF1. The crystal structure of MTERF1 bound to the canonical termination sequence reveals a rare base flipping event that involves the eversion of three nucleotides. These nucleotides are stabilized by stacking interactions with three MTERF1 residues, which are not only essential for base flipping but also for termination activity. To further understand the mechanism of base flipping we examined each of the individual stacking interactions in structural, energetic and functional detail. Individual substitutions of Arg162, Tyr288 and Phe243 have revealed unequal contributions to overall termination activity. Furthermore, our work identifies an important role for Phe322 in the base flipping mechanism and we demonstrate how Phe322 and Phe243 are important for coupling base flipping between the heavy and light strand DNA chains. We propose a step-wise model for the base flipping process that recapitulates our observations. Finally, we show that MTERF1 has the ability to accommodate alternate active conformations. The adaptability of base flipping has implications for MTERF1 function and for the putative function of MTERF1 at alternative binding sites in human mitochondria. Base flipping by MTERF1 can accommodate multiple conformations and occurs in a stepwise fashion.,Byrnes J, Hauser K, Norona L, Mejia E, Simmerling C, Garcia-Diaz M J Mol Biol. 2015 Oct 30. pii: S0022-2836(15)00614-2. doi:, 10.1016/j.jmb.2015.10.021. PMID:26523681[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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