title: Significance of the pathogenic mutation T372R in the Yin Yang 1 protein interaction with DNA--thermodynamic studies.
abstract: This work focuses on the pathogenic missense mutation in YY1 protein correlated with insulinomas. Based on in vitro studies, we demonstrate that the mutation does not affect the secondary structure of either zinc fingers or the N-terminal fragment (NTF) of the protein. Apart from a slight increase in the protein's compactness, no changes in the tertiary structure were observed. The introduced mutation significantly alters DNA-binding properties, both the affinity and enthalpy-entropy contribution of the process, which are highly dependent on the recognized sequence. Obtained results indicate concerted rather than a modular mode of sequence recognition by YY1 with the significant impact of a disordered NTF.
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Nieborak
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Górecki
mesh_terms: D019943:Amino Acid Substitution; D001665:Binding Sites / Q000235:genetics; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005454:Fluorescence Polarization; D006801:Humans; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D050986:YY1 Transcription Factor / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D050505:Mutant Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D004247:DNA
keywords: IDP; Yin Yang 1; carcinogenesis; fluorescence anisotropy; pathogenic variant; zinc fingers