title: Molecular shapes of transcription factors TFIIB and VP16 in solution: implications for recognition.
abstract: The molecular shapes of transcription factors TFIIB and VP16 have been studied by small-angle X-ray scattering (SAXS). We interpret the shapes and discuss the implications for the specific recruitment of these proteins into regulatory assemblies. Human transcription factor TFIIB, a universal component of the transcription preinitiation complex, has a triangular form resulting from intramolecular associations between its two principal structural domains. A segment linking the two domains appears to be conformationally flexible. The solution shape of TFIIB can be well fitted with the crystal structure of the DNA-bound C-terminal domain together with the NMR structure of the N-terminal domain; however, the shape cannot accommodate the NMR structure of the isolated C-terminal domain. We discuss how the conformational differences between the solution structures of the isolated C-terminal domain and the intact protein might result from interdomain allostery. Docking the SAXS shape of intact TFIIB into the preinitiation complex suggests that the flexible linker region may contact the 3' flanking region of the TATA element in the major groove. Transcription rates can be enhanced by activator proteins, and the classical example is the herpes simplex virus factor VP16 (alpha-TIF), which associates with cellular transcription factors, including TFIIB. The shape reconstruction of VP16 from its SAXS profile reveals a globular structural core that can be well modeled by the crystal structure of a conserved, central region of the protein. However, the carboxy terminus extends from this core and is essentially disordered. As it makes defined protein-protein interactions in the activation complex, the flexible segment is likely to condense upon assembly with its partners.
authors.affiliation: Synchrotron Radiation Department, CLRC Daresbury Laboratory, Warrington, Cheshire WA4 4AD, U.K.
authors.forename: J G
authors.initials: JG
authors.lastname: Grossmann
authors.forename: A J
authors.initials: AJ
authors.lastname: Sharff
authors.forename: P
authors.initials: P
authors.lastname: O'Hare
authors.forename: B
authors.initials: B
authors.lastname: Luisi
mesh_terms: D002942:Circular Dichroism; D017405:Herpes Simplex Virus Protein Vmw65 / Q000737:chemistry* / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D012996:Solutions; D035581:Transcription Factor TFIIB; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism* / Q000528:radiation effects; D019065:Virus Assembly; D014965:X-Rays
chemical_list: D017405:Herpes Simplex Virus Protein Vmw65; D012996:Solutions; D035581:Transcription Factor TFIIB; D014157:Transcription Factors