Principles of protein-DNA recognition revealed in the structural analysis of Ndt80-MSE DNA complexes

Structure
Jason S Lamoureux, J N Mark Glover

Abstract

The Saccharomyces cerevisiae transcription factor Ndt80 selectively binds a DNA consensus sequence (the middle sporulation element [MSE]) to activate gene expression after the successful completion of meiotic recombination. Here we report the X-ray crystal structures of Ndt80 bound to ten distinct MSE variants. Comparison of these structures with the structure of Ndt80 bound to a consensus MSE reveals structural principles that determine the DNA binding specificity of this transcription factor. The 5' GC-rich end of the MSE contains distinct 5'-YpG-3' steps that are recognized by arginine side chains through a combination of hydrogen bonding and cation-pi interactions. The 3' AT-rich region is recognized via minor groove contacts that sterically exclude the N2 atom of GC base pairs. The conformation of the AT-rich region is fixed by interactions with the protein that favor recognition of poly(A)-poly(T) versus mixed AT sequences through an avoidance of major groove steric clashes at 5'-ApT-3' steps.

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Citations

Apr 4, 2009·PLoS Computational Biology·Mu Gao, Jeffrey Skolnick
Apr 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Youngchang KimAndrzej Joachimiak
Nov 24, 2011·Nucleic Acids Research·Xueqing ZouKlaus Schulten
Jan 29, 2013·Trends in Biochemical Sciences·Yiwei LiuXiaodong Cheng
May 26, 2015·Biophysical Chemistry·Aleksandra Karolak, Arjan van der Vaart
Jul 12, 2016·Fungal Genetics and Biology : FG & B·Colleen E DoyleBarry J Saville
Mar 24, 2018·The Journal of Biological Chemistry·Ke LiuJinrong Min
Mar 7, 2012·Microbiology and Molecular Biology Reviews : MMBR·Edward Winter

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