title: The transcription factor Spn1 regulates gene expression via a highly conserved novel structural motif.
abstract: Spn1/Iws1 plays essential roles in the regulation of gene expression by RNA polymerase II (RNAPII), and it is highly conserved in organisms ranging from yeast to humans. Spn1 physically and/or genetically interacts with RNAPII, TBP (TATA-binding protein), TFIIS (transcription factor IIS), and a number of chromatin remodeling factors (Swi/Snf and Spt6). The central domain of Spn1 (residues 141-305 out of 410) is necessary and sufficient for performing the essential functions of SPN1 in yeast cells. Here, we report the high-resolution (1.85 Å) crystal structure of the conserved central domain of Saccharomyces cerevisiae Spn1. The central domain is composed of eight α-helices in a right-handed superhelical arrangement and exhibits structural similarity to domain I of TFIIS. A unique structural feature of Spn1 is a highly conserved loop, which defines one side of a pronounced cavity. The loop and the other residues forming the cavity are highly conserved at the amino acid level among all Spn1 family members, suggesting that this is a signature motif for Spn1 orthologs. The locations and the molecular characterization of temperature-sensitive mutations in Spn1 indicate that the cavity is a key attribute of Spn1 that is critical for its regulatory functions during RNAPII-mediated transcriptional activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Pujari
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Radebaugh
authors.forename: Jayanth V
authors.initials: JV
authors.lastname: Chodaparambil
authors.forename: Uma M
authors.initials: UM
authors.lastname: Muthurajan
authors.forename: Adam R
authors.initials: AR
authors.lastname: Almeida
authors.forename: Julie A
authors.initials: JA
authors.lastname: Fischbeck
authors.forename: Karolin
authors.initials: K
authors.lastname: Luger
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Stargell
mesh_terms: D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D005786:Gene Expression Regulation; D008958:Models, Molecular; D020125:Mutation, Missense; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: C475586:SPN1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors