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Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10404-10. doi: 10.1073/pnas.1410110111. Epub 2014 Jul 3.

Structure of a new DNA-binding domain which regulates pathogenesis in a wide variety of fungi.

Author information

1
Departments of Microbiology and Immunology and.
2
Departments of Microbiology and Immunology andDivision of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA 94158.
3
Biochemistry and Biophysics and.
4
Departments of Microbiology and Immunology andBiochemistry and Biophysics and ajohnson@cgl.ucsf.edu.

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.

KEYWORDS:

Candida albicans; fungal pathogenesis; protein–DNA interaction; transcription factor; transcriptional regulation

PMID:
24994900
PMCID:
PMC4115540
DOI:
10.1073/pnas.1410110111
[Indexed for MEDLINE]
Free PMC Article

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