title: Structural models of mammalian mitochondrial transcription factor B2.
abstract: Mammalian mitochondrial DNA (mtDNA) encodes 13 core proteins of oxidative phosphorylation, 12S and 16S ribosomal RNAs, and 22 transfer RNAs. Mutations and deletions of mtDNA and/or nuclear genes encoding mitochondrial proteins have been implicated in a wide range of diseases. Thus, cell survival and health of the organism require some steady-state level of the mitochondrial genome and its expression. In mammalian systems, the mitochondrial transcription factor B2 (mtTFB2 or TFB2M) is indispensable for transcription initiation. TFB2M along with two other proteins, mitochondrial RNA polymerase (mtRNAP or POLRMT) and mitochondrial transcription factor A (mtTFA or TFAM), are key components of the core mitochondrial transcription apparatus. Structural information for POLRMT and TFAM from humans is available; however, there is no available structure for TFB2M. In the present study, three-dimensional structure of TFB2M from humans was modeled using a combination of homology modeling and small-angle X-ray scattering (SAXS). The TFB2M structural model adds substantively to our understanding of TFB2M function. An explanation for the low or absent RNA methyltransferase activity is provided. A putative nucleic acid-binding site is revealed. The amino and carboxy termini, while likely lacking defined secondary structure, appear to adopt compact, globular conformations, thus "capping" the ends of the protein. Finally, sites of interaction of TFB2M with other factors, protein and/or nucleic acid, are suggested by the identification of species-specific clusters on the surface of the protein.
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA. Electronic address: ria2@psu.edu.
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: Moustafa
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Uchida
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Neela
authors.initials: N
authors.lastname: Yennawar
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA. Electronic address: cec9@psu.edu.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Cameron
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D006801:Humans; D008322:Mammals / Q000235:genetics; D008780:Methyltransferases / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae; D053838:Scattering, Small Angle; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics; D014961:X-Ray Diffraction
chemical_list: D024101:Mitochondrial Proteins; D014157:Transcription Factors; D008780:Methyltransferases; C462443:TFB2M protein, human
keywords: Homology modeling; Mitochondria; POLRMT; SAXS; TFAM; TFB2M; Transcription