Indirect DNA Readout by an H-NS Related Protein: Structure of the DNA Complex of the C-Terminal Domain of Ler

PLoS Pathogens

Cristina Madrid¹  Antonio Juárez¹  Pau Bernadó²  Christian Griesinger³  Miquel Pons³  Tiago N. Cordeiro³  Holger Schmidt⁴  Jesús García⁴ 

[1] Department of Microbiology, University of Barcelona, Barcelona, Spain;Institut de Bioenginyeria de Catalunya (IBEC), Parc Científic de Barcelona, Barcelona, Spain;Institute for Research in Biomedicine (IRB Barcelona), Parc Científic de Barcelona, Barcelona, Spain;Max Planck Institute for Biophysical Chemistry, Department of NMR-based Structural Biology, Göttingen, Germany

关键词: DNA structure;    DNA-binding proteins;    Sequence motif analysis;    Anisotropy;    Nuclear Overhauser effect spectroscopy;    Gene regulation;    NMR spectroscopy;    Protein structure;   

DOI  :  10.1371/journal.ppat.1002380

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY