Your browser doesn't support javascript.
loading
Fuzzy recognition by the prokaryotic transcription factor HigA2 from Vibrio cholerae.
Hadzi, San; Zivic, Zala; Kovacic, Matic; Zavrtanik, Uros; Haesaerts, Sarah; Charlier, Daniel; Plavec, Janez; Volkov, Alexander N; Lah, Jurij; Loris, Remy.
Afiliação
  • Hadzi S; Structural Biology Brussels, Department of Biotechnology, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium.
  • Zivic Z; Centre for Structural Biology, VIB, Pleinlaan 2, 1050, Brussels, Belgium.
  • Kovacic M; Department of Physical Chemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000, Ljubljana, Slovenia.
  • Zavrtanik U; Department of Physical Chemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000, Ljubljana, Slovenia.
  • Haesaerts S; Slovenian NMR Center, National Institute of Chemistry, Hajdrihova, 19, 1000, Ljubljana, Slovenia.
  • Charlier D; Department of Physical Chemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000, Ljubljana, Slovenia.
  • Plavec J; Structural Biology Brussels, Department of Biotechnology, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium.
  • Volkov AN; Centre for Structural Biology, VIB, Pleinlaan 2, 1050, Brussels, Belgium.
  • Lah J; Research group of Microbiology, Department of Biotechnology, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium.
  • Loris R; Slovenian NMR Center, National Institute of Chemistry, Hajdrihova, 19, 1000, Ljubljana, Slovenia.
Nat Commun ; 15(1): 3105, 2024 Apr 10.
Article em En | MEDLINE | ID: mdl-38600130
ABSTRACT
Disordered protein sequences can exhibit different binding modes, ranging from well-ordered folding-upon-binding to highly dynamic fuzzy binding. The primary function of the intrinsically disordered region of the antitoxin HigA2 from Vibrio cholerae is to neutralize HigB2 toxin through ultra-high-affinity folding-upon-binding interaction. Here, we show that the same intrinsically disordered region can also mediate fuzzy interactions with its operator DNA and, through interplay with the folded helix-turn-helix domain, regulates transcription from the higBA2 operon. NMR, SAXS, ITC and in vivo experiments converge towards a consistent picture where a specific set of residues in the intrinsically disordered region mediate electrostatic and hydrophobic interactions while "hovering" over the DNA operator. Sensitivity of the intrinsically disordered region to scrambling the sequence, position-specific contacts and absence of redundant, multivalent interactions, point towards a more specific type of fuzzy binding. Our work demonstrates how a bacterial regulator achieves dual functionality by utilizing two distinct interaction modes within the same disordered sequence.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vibrio cholerae / Proteínas Intrinsicamente Desordenadas Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vibrio cholerae / Proteínas Intrinsicamente Desordenadas Idioma: En Ano de publicação: 2024 Tipo de documento: Article