title: Indirect DNA readout by an H-NS related protein: structure of the DNA complex of the C-terminal domain of Ler.
abstract: Ler, a member of the H-NS protein family, is the master regulator of the LEE pathogenicity island in virulent Escherichia coli strains. Here, we determined the structure of a complex between the DNA-binding domain of Ler (CT-Ler) and a 15-mer DNA duplex. CT-Ler recognizes a preexisting structural pattern in the DNA minor groove formed by two consecutive regions which are narrower and wider, respectively, compared with standard B-DNA. The compressed region, associated with an AT-tract, is sensed by the side chain of Arg90, whose mutation abolishes the capacity of Ler to bind DNA. The expanded groove allows the approach of the loop in which Arg90 is located. This is the first report of an experimental structure of a DNA complex that includes a protein belonging to the H-NS family. The indirect readout mechanism not only explains the capacity of H-NS and other H-NS family members to modulate the expression of a large number of genes but also the origin of the specificity displayed by Ler. Our results point to a general mechanism by which horizontally acquired genes may be specifically recognized by members of the H-NS family.
authors: Institute for Research in Biomedicine (IRB Barcelona), Parc Científic de Barcelona, Barcelona, Spain.
authors: Tiago N
authors: TN
authors: Cordeiro
authors: Holger
authors: H
authors: Schmidt
authors: Cristina
authors: C
authors: Madrid
authors: Antonio
authors: A
authors: Juárez
authors: Pau
authors: P
authors: Bernadó
authors: Christian
authors: C
authors: Griesinger
authors: Jesús
authors: J
authors: García
authors: Miquel
authors: M
authors: Pons
mesh_terms: D001120:Arginine / Q000378:metabolism; D059371:DNA, B-Form / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry; D004926:Escherichia coli / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D036781:Fimbriae Proteins / Q000737:chemistry / Q000502:physiology*; D022761:Gene Transfer, Horizontal; D044404:Genomic Islands; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*
chemical_list: D059371:DNA, B-Form; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C529458:FimG protein, E coli; C465556:Ler protein, E coli; D015534:Trans-Activators; D036781:Fimbriae Proteins; D001120:Arginine