title: Structural basis for recognition and remodeling of the TBP:DNA:NC2 complex by Mot1.
abstract: Swi2/Snf2 ATPases remodel substrates such as nucleosomes and transcription complexes to control a wide range of DNA-associated processes, but detailed structural information on the ATP-dependent remodeling reactions is largely absent. The single subunit remodeler Mot1 (modifier of transcription 1) dissociates TATA box-binding protein (TBP):DNA complexes, offering a useful system to address the structural mechanisms of Swi2/Snf2 ATPases. Here, we report the crystal structure of the N-terminal domain of Mot1 in complex with TBP, DNA, and the transcription regulator negative cofactor 2 (NC2). Our data show that Mot1 reduces DNA:NC2 interactions and unbends DNA as compared to the TBP:DNA:NC2 state, suggesting that Mot1 primes TBP:NC2 displacement in an ATP-independent manner. Electron microscopy and cross-linking data suggest that the Swi2/Snf2 domain of Mot1 associates with the upstream DNA and the histone fold of NC2, thereby revealing parallels to some nucleosome remodelers. This study provides a structural framework for how a Swi2/Snf2 ATPase interacts with its substrate DNA:protein complex.
authors.affiliation: Gene Center, Department of Biochemistry, Ludwig Maximilian University, Munich, Germany.
authors.forename: Agata
authors.initials: A
authors.lastname: Butryn
authors.affiliation: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried, , Germany.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Schuller
authors.affiliation: Gene Center, Department of Biochemistry, Ludwig Maximilian University, Munich, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Stoehr
authors.affiliation: Gene Center, Department of Biochemistry, Ludwig Maximilian University, Munich, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Runge-Wollmann
authors.affiliation: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried, , Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Förster
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, United States.
authors.forename: David T
authors.initials: DT
authors.lastname: Auble
authors.affiliation: Gene Center, Department of Biochemistry, Ludwig Maximilian University, Munich, Germany.
authors.forename: Karl-Peter
authors.identifier: http://orcid.org/0000-0002-4528-8357
authors.initials: KP
authors.lastname: Hopfner
mesh_terms: D018360:Crystallography, X-Ray; D004271:DNA, Fungal / Q000737:chemistry / Q000378:metabolism*; D009670:Encephalitozoon cuniculi / Q000502:physiology*; D008854:Microscopy, Electron; D008958:Models, Molecular; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D035381:TATA-Binding Protein Associated Factors / Q000737:chemistry / Q000378:metabolism*; D035181:TATA-Box Binding Protein / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D010750:Phosphoproteins; D035381:TATA-Binding Protein Associated Factors; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; C075995:down-regulator of transcription 1
keywords: Mot1; NC2; Swi2/Snf2; TBP; biophysics; encephalitozoon cuniculi; hybrid methods; structural biology; transcription regulation