title: Structure of a new DNA-binding domain which regulates pathogenesis in a wide variety of fungi.
abstract: WOPR-domain proteins are found throughout the fungal kingdom where they function as master regulators of cell morphology and pathogenesis. Genetic and biochemical experiments previously demonstrated that these proteins bind to specific DNA sequences and thereby regulate transcription. However, their primary sequence showed no relationship to any known DNA-binding domain, and the basis for their ability to recognize DNA sequences remained unknown. Here, we describe the 2.6-Å crystal structure of a WOPR domain in complex with its preferred DNA sequence. The structure reveals that two highly conserved regions, separated by an unconserved linker, form an interdigitated β-sheet that is tilted into the major groove of DNA. Although the main interaction surface is in the major groove, the highest-affinity interactions occur in the minor groove, primarily through a deeply penetrating arginine residue. The structure reveals a new, unanticipated mechanism by which proteins can recognize specific sequences of DNA.
authors.affiliation: Departments of Microbiology and Immunology and.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Lohse
authors.affiliation: Departments of Microbiology and Immunology andDivision of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA 94158.
authors.forename: Oren S
authors.initials: OS
authors.lastname: Rosenberg
authors.affiliation: Departments of Microbiology and Immunology and.
authors.forename: Jeffery S
authors.initials: JS
authors.lastname: Cox
authors.affiliation: Biochemistry and Biophysics and.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stroud
authors.affiliation: Biochemistry and Biophysics and.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Finer-Moore
authors.affiliation: Departments of Microbiology and Immunology andBiochemistry and Biophysics and ajohnson@cgl.ucsf.edu.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Johnson
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D018360:Crystallography, X-Ray; D004271:DNA, Fungal / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism*; D005658:Fungi / Q000378:metabolism / Q000472:pathogenicity*; D015966:Gene Expression Regulation, Fungal; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D000596:Amino Acids; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators
keywords: Candida albicans; fungal pathogenesis; protein–DNA interaction; transcription factor; transcriptional regulation