title: Structures of the Escherichia coli transcription activator and regulator of diauxie, XylR: an AraC DNA-binding family member with a LacI/GalR ligand-binding domain.
abstract: Escherichia coli can rapidly switch to the metabolism of l-arabinose and d-xylose in the absence of its preferred carbon source, glucose, in a process called carbon catabolite repression. Transcription of the genes required for l-arabinose and d-xylose consumption is regulated by the sugar-responsive transcription factors, AraC and XylR. E. coli represents a promising candidate for biofuel production through the metabolism of hemicellulose, which is composed of d-xylose and l-arabinose. Understanding the l-arabinose/d-xylose regulatory network is key for such biocatalyst development. Unlike AraC, which is a well-studied protein, little is known about XylR. To gain insight into XylR function, we performed biochemical and structural studies. XylR contains a C-terminal AraC-like domain. However, its N-terminal d-xylose-binding domain contains a periplasmic-binding protein (PBP) fold with structural homology to LacI/GalR transcription regulators. Like LacI/GalR proteins, the XylR PBP domain mediates dimerization. However, unlike LacI/GalR proteins, which dimerize in a parallel, side-to-side manner, XylR PBP dimers are antiparallel. Strikingly, d-xylose binding to this domain results in a helix to strand transition at the dimer interface that reorients both DNA-binding domains, allowing them to bind and loop distant operator sites. Thus, the combined data reveal the ligand-induced activation mechanism of a new family of DNA-binding proteins.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Ni
authors.forename: Nam K
authors.initials: NK
authors.lastname: Tonthat
authors.forename: Nagababu
authors.initials: N
authors.lastname: Chinnam
authors.forename: Maria A
authors.initials: MA
authors.lastname: Schumacher
mesh_terms: D004269:DNA, Bacterial / Q000378:metabolism / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D056968:Lac Repressors / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014994:Xylose / Q000737:chemistry / Q000378:metabolism
chemical_list: D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C050993:Galactose repressor proteins; D056968:Lac Repressors; D012097:Repressor Proteins; D014157:Transcription Factors; C579718:XylR protein, E coli; D014994:Xylose