title: The transcriptional repressor RYBP is a natively unfolded protein which folds upon binding to DNA.
abstract: RYBP (Ring1A and YY1 binding protein) is a zinc finger protein with an essential role during embryonic development, which binds transcriptional factors, Polycomb products, and mediators of apoptosis, suggesting roles in, apparently, unrelated functions. To investigate mechanisms underlying its association with functionally diverse partners, we set out to study its structural properties using a number of biophysical (fluorescence, circular dichroism, Fourier transform infrared, and NMR spectroscopies) and hydrodynamic (analytical ultracentrifugation, DOSY-NMR, and gel filtration chromatography) techniques. We find RYBP to be a noncompact protein with little residual secondary structure, lacking a well-defined tertiary structure. These observations are also supported by theoretical calculations using neural networks and pairwise energy content, suggesting that RYBP is a natively unfolded protein. In addition, structural studies on its binding to the C-terminal region of the Polycomb protein Ring1B or to DNA show conformational changes in the complexed RYBP, consistent with the acquisition of a folded structure. The data provide a structural explanation for RYBP engagement in functionally unrelated pathways by means of its assembly into various macromolecular complexes as an unstructured protein with the ability to acquire a well-structured fold due to its association with different partners.
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante), Spain. jlneira@umh.es
authors.forename: José L
authors.initials: JL
authors.lastname: Neira
authors.forename: Mónica
authors.initials: M
authors.lastname: Román-Trufero
authors.forename: Lellys M
authors.initials: LM
authors.lastname: Contreras
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Singh
authors.forename: Francisco N
authors.initials: FN
authors.lastname: Barrera
authors.forename: M Lourdes
authors.initials: ML
authors.lastname: Renart
authors.forename: Miguel
authors.initials: M
authors.lastname: Vidal
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D019295:Computational Biology; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005453:Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D014364:Tryptophan / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; D014364:Tryptophan; D004247:DNA