title: A Three-protein Charge Zipper Stabilizes a Complex Modulating Bacterial Gene Silencing.
abstract: The Hha/YmoA nucleoid-associated proteins help selectively silence horizontally acquired genetic material, including pathogenicity and antibiotic resistance genes and their maintenance in the absence of selective pressure. Members of the Hha family contribute to gene silencing by binding to the N-terminal dimerization domain of H-NS and modifying its selectivity. Hha-like proteins and the H-NS N-terminal domain are unusually rich in charged residues, and their interaction is mostly electrostatic-driven but, nonetheless, highly selective. The NMR-based structural model of the complex between Hha/YmoA and the H-NS N-terminal dimerization domain reveals that the origin of the selectivity is the formation of a three-protein charge zipper with interdigitated complementary charged residues from Hha and the two units of the H-NS dimer. The free form of YmoA shows collective microsecond-millisecond dynamics that can by measured by NMR relaxation dispersion experiments and shows a linear dependence with the salt concentration. The number of residues sensing the collective dynamics and the population of the minor form increased in the presence of H-NS. Additionally, a single residue mutation in YmoA (D43N) abolished H-NS binding and the dynamics of the apo-form, suggesting the dynamics and binding are functionally related.
authors.affiliation: From the Biomolecular NMR Laboratory, Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain, Centre de Biochimie Structurale, INSERM U1054, CNRS UMR 5048, Université Montpellier 1 and 2, 34092 Montpellier, France.
authors.forename: Tiago N
authors.initials: TN
authors.lastname: Cordeiro
authors.affiliation: Institute for Research in Biomedicine (IRB-Barcelona), 08028 Barcelona, Spain, and.
authors.forename: Jesús
authors.initials: J
authors.lastname: García
authors.affiliation: Centre de Biochimie Structurale, INSERM U1054, CNRS UMR 5048, Université Montpellier 1 and 2, 34092 Montpellier, France.
authors.forename: Pau
authors.initials: P
authors.lastname: Bernadó
authors.affiliation: the Structural Biology Unit, Center for Cooperative Research in Biosciences (CIC-bioGUNE), 48160 Elexalde, Derio, Spain omillet@cicbiogune.es.
authors.forename: Oscar
authors.initials: O
authors.lastname: Millet
authors.affiliation: From the Biomolecular NMR Laboratory, Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain, mpons@ub.edu.
authors.forename: Miquel
authors.initials: M
authors.lastname: Pons
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004755:Enterobacteriaceae / Q000235:genetics* / Q000378:metabolism*; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D022761:Gene Transfer, Horizontal; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D060066:Protein Interaction Maps; D055503:Protein Multimerization; D055672:Static Electricity
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins
keywords: charge zipper complexes; electrostatics; gene silencing; horizontal gene transfer; nuclear magnetic resonance (NMR); nucleoid-associated proteins; protein dynamic; protein-protein interaction