Crystal structure of the transcription factor sc-mtTFB offers insights into mitochondrial transcription

Although it is commonly accepted that binding of mitochondrial transcriptio n factor sc-mtTFB to the mitochondrial RNA polymerase is required for speci fic transcription initiation in Saccharomyces cerevisiae, its precise role has remained undefined. In the present work, the crystal structure of sc-mt TFB has been determined to 2.6 Angstrom resolution. The protein consists of two domains, an N-terminal alpha/beta -domain and a smaller domain made up of four alpha -helices. Contrary to previous predictions, sc-mtTFB does no t resemble Escherichia coli sigma -factors but rather is structurally homol ogous to rRNA methyltransferase ErmC'. This suggests that sc-mtTFB function s as an RNA-binding protein, an observation standing in contradiction to th e existing model, which proposed a direct interaction of sc-mtTFB with the mitochondrial DNA promoter. Based on the structure, we propose that the pro moter specificity region is located on the mitochondrial RNA polymerase and that binding of sc-mtTFB indirectly mediates interaction of the core enzym e with the promoter site.