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.
Highlights
Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) are causal agents of infectious diarrhea
Pathogenic Escherichia coli strains and other enterobacteria carry genes acquired from other bacteria by a process known as horizontal gene transfer
Ler is a member of the H-NS family that competes with H-NS to activate the expression of a group of horizontally acquired genes that encode for a molecular machine used by E. coli to infect human cells
Summary
Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) are causal agents of infectious diarrhea. While the former is responsible mainly for infantile diarrhea, EHEC infections are associated with hemorrhagic colitis and may produce a life-threatening complication known as hemolytic uremic syndrome. The genes required for the formation of A/E lesions are clustered on a pathogenicity island known as the locus of enterocyte effacement (LEE). The first gene of the LEE1 operon encodes the LEE-encoded regulator Ler, which is essential for the formation of A/E lesions in infected cells [3,4] and for the in vivo virulence of A/E pathogenic E. coli strains [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
