title: New Insights into Cooperative Binding of Homeodomain Transcription Factors PREP1 and PBX1 to DNA.
abstract: PREP1 and PBX1 are homeodomain (HD) transcription factors that play crucial roles in embryonic development. Here, we present the first biophysical characterization of a PREP1 HD, and the NMR spectroscopic study of its DNA binding pocket. The data show that residues flanking the HD participate in DNA binding. The kinetic parameters for DNA binding of individual PREP1 and PBX1 HDs, and of their combination, show that isolated PREP1 and PBX1 HDs bind to DNA in a cooperative manner. A novel PREP1 motif, flanking the HD at the C-terminus, is required for cooperativity.
authors.affiliation: Biomolecular NMR Unit, S. Raffaele Scientific Institute, via Olgettina 60, 20133, Milano, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zucchelli
authors.affiliation: IFOM (Foundation for Italian Cancer Research Institute of Molecular Oncology), via Adamello 16, 20139, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ferrari
authors.affiliation: IFOM (Foundation for Italian Cancer Research Institute of Molecular Oncology), via Adamello 16, 20139, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.affiliation: Biomolecular NMR Unit, S. Raffaele Scientific Institute, via Olgettina 60, 20133, Milano, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Musco
authors.affiliation: IFOM (Foundation for Italian Cancer Research Institute of Molecular Oncology), via Adamello 16, 20139, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bruckmann
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D004247:DNA / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D000075062:Pre-B-Cell Leukemia Transcription Factor 1 / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C106682:PKNOX1 protein, human; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011994:Recombinant Proteins; D014157:Transcription Factors; D004247:DNA