Structure of a Leu3-DNA complex: recognition of everted CGG half-sites by a Zn2Cys6 binuclear cluster protein

Structure
Mary X FitzgeraldR Marmorstein

Abstract

Gal4 is the prototypical Zn2Cys6 binuclear cluster transcriptional regulator that binds as a homodimer to DNA containing inverted CGG half-sites. Leu3, a member of this protein family, binds to everted (opposite polarity to inverted) CGG half-sites, and an H50C mutation within the Leu3 Zn2Cys6 binuclear motif abolishes its transcriptional repression function without impairing DNA binding. We report the X-ray crystal structures of DNA complexes with Leu3 and Leu3(H50C) and solution DNA binding studies of selected Leu3 mutant proteins. These studies reveal the molecular details of everted CGG half-site recognition, and suggest a role for the H50C mutation in transcriptional repression. Comparison with the Gal4-DNA complex shows an unexpected conservation in the DNA recognition mode of inverted and everted CGG half-sites, and points to a critical function of a linker region between the Zn2Cys6 binuclear cluster and dimerization regions in DNA binding specificity. Broader implications of these findings are discussed.

References

Apr 2, 1992·Nature·R MarmorsteinS C Harrison
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Jan 1, 1990·Archives of Biochemistry and Biophysics·M H PetersG B Kohlhaw
Jan 25, 1990·Nucleic Acids Research·K M ZhouG B Kohlhaw
Sep 1, 1989·Molecular and Cellular Biology·P FridenP Schimmel
Aug 1, 1994·Molecular and Cellular Biology·E Remboutsika, G B Kohlhaw
Jun 1, 1997·Fungal Genetics and Biology : FG & B·R B Todd, A Andrianopoulos
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Feb 17, 2001·Current Opinion in Structural Biology·F Rastinejad
Feb 24, 2001·Journal of Molecular Biology·K Phillips, B Luisi
Apr 26, 2002·Molecular Microbiology·Dennis GómezClaudio Scazzocchio
May 5, 2004·The Journal of Biological Chemistry·Bassel AkacheBernard Turcotte
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Sep 9, 2006·Microbiology and Molecular Biology Reviews : MMBR·Sarah MacPhersonBernard Turcotte
Sep 19, 2007·Molecular and Cellular Biology·Nitnipa SoontorngunBernard Turcotte
Jul 10, 2008·Structure·Manqing HongRonen Marmorstein
Nov 14, 2007·Structure·John J BellizziStephen C Harrison
Jul 5, 2012·PloS One·Ivana Petrovska, Carol A Kumamoto
Aug 9, 2008·The Biochemical Journal·Robert N CampbellRichard J Reece

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