| Structural highlights
Function
WOR1_CANAL Master transcriptional regulator of the switch between 2 heritable states, the white and opaque states. These 2 cell types differ in many characteristics, including cell structure, mating competence, and virulence. Each state is heritable for many generations, and switching between states occurs stochastically, at low frequency. WOR1 Binds the intergenic regions upstream of the genes encoding three additional transcriptional regulators of white-opaque switching, CZF1, EFG1, and WOR2. Phenotypic switching from the white to the opaque phase is a necessary step for mating. Plays a role in cell adhesion and pseudohyphal growth.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
Wor1 (white-opaque switching regulator 1) is a master regulator of the white-opaque switching in Candida albicans, an opportunistic human fungal pathogen, and is associated with its pathogenicity and commensality. Wor1 contains a conserved DNA-binding region at the N-terminus, consisting of two conserved segments (WOPRa and WOPRb) connected by a non-conserved linker that can bind to specific DNA sequences of the promoter regions and then regulates the transcription. Here, we report the crystal structure of the C. albicans Wor1 WOPR segments in complex with a double-stranded DNA corresponding to one promoter region of WOR1. The sequentially separated WOPRa and WOPRb are structurally interwound together to form a compact globular domain that we term the WOPR domain. The WOPR domain represents a new conserved fungal-specific DNA-binding domain which uses primarily a conserved loop to recognize and interact specifically with a conserved 6-bp motif of the DNA in both minor and major grooves. The protein-DNA interactions are essential for WOR1 transcriptional regulation and white-to-opaque switching. The structural and biological data together reveal the molecular basis for the recognition and binding specificity of the WOPR domain with its specific DNA sequences and the function of Wor1 in the activation of transcription.Cell Research advance online publication 5 August 2014; doi:10.1038/cr.2014.102.
Crystal structure of the WOPR-DNA complex and implications for Wor1 function in white-opaque switching of Candida albicans.,Zhang S, Zhang T, Yan M, Ding J, Chen J Cell Res. 2014 Aug 5. doi: 10.1038/cr.2014.102. PMID:25091450[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li F, Palecek SP. Identification of Candida albicans genes that induce Saccharomyces cerevisiae cell adhesion and morphogenesis. Biotechnol Prog. 2005 Nov-Dec;21(6):1601-9. PMID:16321041 doi:https://dx.doi.org/10.1021/bp050236c
- ↑ Srikantha T, Borneman AR, Daniels KJ, Pujol C, Wu W, Seringhaus MR, Gerstein M, Yi S, Snyder M, Soll DR. TOS9 regulates white-opaque switching in Candida albicans. Eukaryot Cell. 2006 Oct;5(10):1674-87. Epub 2006 Sep 1. PMID:16950924 doi:https://dx.doi.org/10.1128/EC.00252-06
- ↑ Zordan RE, Galgoczy DJ, Johnson AD. Epigenetic properties of white-opaque switching in Candida albicans are based on a self-sustaining transcriptional feedback loop. Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12807-12. Epub 2006 Aug 9. PMID:16899543 doi:https://dx.doi.org/10.1073/pnas.0605138103
- ↑ Huang G, Wang H, Chou S, Nie X, Chen J, Liu H. Bistable expression of WOR1, a master regulator of white-opaque switching in Candida albicans. Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12813-8. Epub 2006 Aug 11. PMID:16905649 doi:https://dx.doi.org/10.1073/pnas.0605270103
- ↑ Zordan RE, Miller MG, Galgoczy DJ, Tuch BB, Johnson AD. Interlocking transcriptional feedback loops control white-opaque switching in Candida albicans. PLoS Biol. 2007 Oct;5(10):e256. PMID:17880264 doi:https://dx.doi.org/10.1371/journal.pbio.0050256
- ↑ Ramirez-Zavala B, Reuss O, Park YN, Ohlsen K, Morschhauser J. Environmental induction of white-opaque switching in Candida albicans. PLoS Pathog. 2008 Jun 13;4(6):e1000089. doi: 10.1371/journal.ppat.1000089. PMID:18551173 doi:https://dx.doi.org/10.1371/journal.ppat.1000089
- ↑ Lohse MB, Johnson AD. Temporal anatomy of an epigenetic switch in cell programming: the white-opaque transition of C. albicans. Mol Microbiol. 2010 Oct;78(2):331-43. doi: 10.1111/j.1365-2958.2010.07331.x. Epub, 2010 Aug 29. PMID:20735781 doi:https://dx.doi.org/10.1111/j.1365-2958.2010.07331.x
- ↑ Cain CW, Lohse MB, Homann OR, Sil A, Johnson AD. A conserved transcriptional regulator governs fungal morphology in widely diverged species. Genetics. 2012 Feb;190(2):511-21. doi: 10.1534/genetics.111.134080. Epub 2011 Nov, 17. PMID:22095082 doi:https://dx.doi.org/10.1534/genetics.111.134080
- ↑ Du H, Guan G, Xie J, Cottier F, Sun Y, Jia W, Muhlschlegel FA, Huang G. The transcription factor Flo8 mediates CO2 sensing in the human fungal pathogen Candida albicans. Mol Biol Cell. 2012 Jul;23(14):2692-701. doi: 10.1091/mbc.E12-02-0094. Epub 2012 , May 23. PMID:22621896 doi:https://dx.doi.org/10.1091/mbc.E12-02-0094
- ↑ Zhang S, Zhang T, Yan M, Ding J, Chen J. Crystal structure of the WOPR-DNA complex and implications for Wor1 function in white-opaque switching of Candida albicans. Cell Res. 2014 Aug 5. doi: 10.1038/cr.2014.102. PMID:25091450 doi:https://dx.doi.org/10.1038/cr.2014.102
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