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

Matthew B. Lohse; Oren S. Rosenberg; Jeffery S. CoxRobert M. StroudJanet S. Finer-MooreAlexander D. Johnson

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

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

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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-? 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.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第29期|10404-10410|共7页
作者
Matthew B. Lohse; Oren S. Rosenberg; Jeffery S. CoxRobert M. StroudJanet S. Finer-MooreAlexander D. Johnson;
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作者单位

Departments of Microbiology and Immunology, Department of Medicine, University of California, San Francisco, CA 94158;

Biochemistry and Biophysics, Department of Medicine, University of California, San Francisco, CA 94158;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
fungal pathogenesis; transcription factor; transcriptional regulation; protein–DNA interaction; Candida albicans;

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

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