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| Subject Categories: Signal Transduction | Structural Biology |
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| The EMBO Journal
(2007) 26, 5153–5166, doi:10.1038/sj.emboj.7601918 Published online 22 November 2007 |
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| The structural basis of cyclic diguanylate signal transduction by PilZ domains |
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| Jordi Benach1, 4, Swarup S Swaminathan1, 4, Rita Tamayo2, Samuel K Handelman1, Ewa Folta-Stogniew3, John E Ramos1, Farhad Forouhar1, Helen Neely1, Jayaraman Seetharaman1, Andrew Camilli2 and John F Hunt1 |
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1 Department of Biological Sciences, Northeast Structural Genomics Consortium, Columbia University, New York, NY, USA 2 Department of Molecular Biology & Microbiology, the Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, MA, USA 3 WM Keck Biotechnology Research Laboratory, Yale University School of Medicine, New Haven, CT, USA To whom correspondence should be addressed John F Hunt, Department of Biological Sciences, Northeast Structural Genomics Consortium, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA. Tel.: +1 212 854 5443; Fax: +1 212 865 8246; E-mail: jfhunt@biology.columbia.edu 4 These authors contributed equally to this work Received 15 March 2007; Accepted 18 October 2007; Published online 22 November 2007. |
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| Abstract |
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The second messenger cyclic diguanylate (c-di-GMP) controls the transition between motile and sessile growth in eubacteria, but little is known about the proteins that sense its concentration. Bioinformatics analyses suggested that PilZ domains bind c-di-GMP and allosterically modulate effector pathways. We have determined a 1.9 Å crystal structure of c-di-GMP bound to VCA0042/PlzD, a PilZ domain-containing protein from Vibrio cholerae. Either this protein or another specific PilZ domain-containing protein is required for V. cholerae to efficiently infect mice. VCA0042/PlzD comprises a C-terminal PilZ domain plus an N-terminal domain with a similar  -barrel fold. C-di-GMP contacts seven of the nine strongly conserved residues in the PilZ domain, including three in a seven-residue long N-terminal loop that undergoes a conformational switch as it wraps around c-di-GMP. This switch brings the PilZ domain into close apposition with the N-terminal domain, forming a new allosteric interaction surface that spans these domains and the c-di-GMP at their interface. The very small size of the N-terminal conformational switch is likely to explain the facile evolutionary diversification of the PilZ domain. |
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| Keywords: allostery, bacterial pathogenesis, cyclic diguanylate (cyclic-di-GMP), fluorescence resonance energy transfer, X-ray crystallography |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe structural basis of cyclic diguanylate signal transduction by PilZ domains The EMBO Journal Article Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid Nature Letters to Editor (15 Jan 1987) Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid Nature Letters to Editor (15 Jan 1987) |
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