Control of DNA minor groove width and Fis protein binding by the purine 2-amino group

The width of the DNA minor groove varies with sequence and can be a major determinant of DNA shape recognition by proteins. For example, the minor groove within the center of the Fis–DNA complex narrows to about half the mean minor groove width of canonical B-form DNA to fit onto the protein surface. G/C base pairs within this segment, which is not contacted by the Fis protein, reduce binding affinities up to 2000-fold over A/T-rich sequences. We show here through multiple X-ray structures and binding properties of Fis–DNA complexes containing base analogs that the 2-amino group on guanine is the primary molecular determinant controlling minor groove widths. Molecular dynamics simulations of free-DNA targets with canonical and modified bases further demonstrate that sequence-dependent narrowing of minor groove widths is modulated almost entirely by the presence of purine 2-amino groups. We also provide evidence that protein-mediated phosphate neutralization facilitates minor groove compression and is particularly important for binding to non-optimally shaped DNA duplexes.

[1]  Richard E. Dickerson,et al.  Crystal structure analysis of a complete turn of B-DNA , 1980, Nature.

[2]  Tamar Schlick,et al.  Innovations in biomolecular modeling and simulation: Volumes 1 and 2 , 2012 .

[3]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[4]  G. Hong,et al.  Nucleic Acids Research , 2015, Nucleic Acids Research.

[5]  N. Seeman,et al.  Sequence-specific Recognition of Double Helical Nucleic Acids by Proteins (base Pairs/hydrogen Bonding/recognition Fidelity/ion Binding) , 2022 .

[6]  D. Hamelberg,et al.  Effect of a neutralized phosphate backbone on the minor groove of B-DNA: molecular dynamics simulation studies. , 2002, Nucleic acids research.

[7]  Phoebe A Rice,et al.  Integration host factor: putting a twist on protein-DNA recognition. , 2003, Journal of molecular biology.

[8]  L. J. Maher,et al.  Electrostatic mechanisms of DNA deformation. , 2000, Annual review of biophysics and biomolecular structure.

[9]  G. Murshudov,et al.  Refinement of macromolecular structures by the maximum-likelihood method. , 1997, Acta crystallographica. Section D, Biological crystallography.

[10]  S. Neidle.  Oxford handbook of nucleic acid structure , 1998 .

[11]  Paul Carlson,et al.  DNA twisting and the effects of non-contacted bases on affinity of 434 operator for 434 represser , 1992, Nature.

[12]  J. Šponer,et al.  Refinement of the AMBER Force Field for Nucleic Acids: Improving the Description of α/γ Conformers , 2007 .

[13]  Daniel Svozil,et al.  Refinement of the AMBER force field for nucleic acids: improving the description of alpha/gamma conformers. , 2007, Biophysical journal.

[14]  R. C. Johnson,et al.  The Fis protein: it's not just for DNA inversion anymore , 1992, Molecular microbiology.

[15]  T. Haran,et al.  The unique structure of A-tracts and intrinsic DNA bending , 2009, Quarterly Reviews of Biophysics.

[16]  M. Churchill,et al.  The high mobility group box: the ultimate utility player of a cell. , 2012, Trends in biochemical sciences.

[17]  Loren Dean Williams,et al.  Sequence recognition of DNA by protein-induced conformational transitions. , 2010, Journal of molecular biology.

[18]  Milton H Saier,et al.  The Bacterial Chromosome , 2008, Critical reviews in biochemistry and molecular biology.

[19]  R. Mann,et al.  The role of DNA shape in protein-DNA recognition , 2009, Nature.

[20]  L. Williams,et al.  High-resolution structure of an extended A-tract: [d(CGCAAATTTGCG)]2. , 2004, Journal of the American Chemical Society.

[21]  R. Hegde,et al.  The Structural Basis of DNA Target Discrimination by Papillomavirus E2 Proteins* , 2000, The Journal of Biological Chemistry.

[22]  F. Javier Luque,et al.  Towards a molecular dynamics consensus view of B-DNA flexibility , 2008, Nucleic acids research.

[23]  T. Steitz,et al.  Protein-nucleic acid interactions. , 2001, Current opinion in structural biology.

[24]  Nicholas M. Luscombe,et al.  Amino acid?base interactions: a three-dimensional analysis of protein?DNA interactions at an atomic level , 2001, Nucleic Acids Res..

[25]  Stephen C. J. Parker,et al.  A map of minor groove shape and electrostatic potential from hydroxyl radical cleavage patterns of DNA. , 2011, ACS chemical biology.

[26]  C. Dorman.  Nucleoid-associated proteins and bacterial physiology. , 2009, Advances in applied microbiology.

[27]  Duilio Cascio,et al.  The shape of the DNA minor groove directs binding by the DNA-bending protein Fis. , 2010, Genes & development.

[28]  A M Gronenborn,et al.  Minor groove-binding architectural proteins: structure, function, and DNA recognition. , 1998, Annual review of biophysics and biomolecular structure.

[29]  M. Schumacher,et al.  Crystal structure of LacI member, PurR, bound to DNA: minor groove binding by alpha helices. , 1994, Science.

[30]  F. J. Luque,et al.  The effect of amino groups on the stability of DNA duplexes and triplexes based on purines derived from inosine. , 2001, Nucleic acids research.

[31]  Randy J Read,et al.  Electronic Reprint Biological Crystallography Phenix: Building New Software for Automated Crystallographic Structure Determination Biological Crystallography Phenix: Building New Software for Automated Crystallographic Structure Determination , 2022 .

[32]  Daniele Varsano,et al.  Optical properties of triplex DNA from time-dependent density functional theory. , 2012, The journal of physical chemistry. B.

[33]  Yongping Shao,et al.  Functional characterization of the Escherichia coli Fis-DNA binding sequence. , 2008, Journal of molecular biology.

[34]  S Neidle,et al.  DNA minor-groove recognition by small molecules. , 2001, Natural product reports.

[35]  Yongping Shao,et al.  Biochemical identification of base and phosphate contacts between Fis and a high-affinity DNA binding site. , 2008, Journal of molecular biology.

[36]  G. Ciccotti,et al.  Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes , 1977 .

[37]  Wei Yang,et al.  Protein–nucleic acid interactions , 2004 .

[38]  F. J. Luque,et al.  Dynamics of B-DNA on the microsecond time scale. , 2007, Journal of the American Chemical Society.

[39]  J. Šponer,et al.  Molecular dynamics of DNA quadruplex molecules containing inosine, 6-thioguanine and 6-thiopurine. , 2001, Biophysical journal.

[40]  W. Olson,et al.  3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures. , 2003, Nucleic acids research.

[41]  R. C. Johnson,et al.  Variable structures of Fis-DNA complexes determined by flanking DNA-protein contacts. , 1996, Journal of molecular biology.

[42]  Reid C. Johnson,et al.  Major Nucleoid Proteins in the Structure and Function of the Escherichia coli Chromosome , 2005 .

[43]  Steven A Mauro,et al.  The Role of the Minor Groove Substituents in Indirect Readout of DNA Sequence by 434 Repressor* , 2003, The Journal of Biological Chemistry.

[44]  L. Williams,et al.  DNA structure: cations in charge? , 1999, Current opinion in structural biology.

[45]  I. Weber,et al.  Crystal structure of a B-DNA dodecamer containing inosine, d(CGCIAATTCGCG), at 2.4 A resolution and its comparison with other B-DNA dodecamers. , 1992, Nucleic acids research.

[46]  R. Lavery,et al.  Defining the structure of irregular nucleic acids: conventions and principles. , 1989, Journal of biomolecular structure & dynamics.

[47]  M. Riley,et al.  The Bacterial Chromosome , 1990 .

[48]  R. Dickerson,et al.  Structure of the B-DNA decamer C-C-A-A-C-I-T-T-G-G in two different space groups: conformational flexibility of B-DNA. , 1993, Biochemistry.

[49]  Michael A. Crickmore,et al.  Functional Specificity of a Hox Protein Mediated by the Recognition of Minor Groove Structure , 2007, Cell.

[50]  Janez Plavec,et al.  A unified model for the origin of DNA sequence-directed curvature. , 2003, Biopolymers.

[51]  M. Kimmel,et al.  Conflict of interest statement. None declared. , 2010 .

[52]  Reid C. Johnson,et al.  Chapter 8:Bending and Compaction of DNA by Proteins , 2008 .

[53]  The molecular structure of wild-type and a mutant Fis protein: relationship between mutational changes and recombinational enhancer function or DNA binding. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[54]  W. Saenger,et al.  Three-dimensional structure of the E. coli DMA-binding protein FIS , 1991, Nature.

[55]  S. McLeod,et al.  Mechanism of chromosome compaction and looping by the Escherichia coli nucleoid protein Fis. , 2006, Journal of molecular biology.

[56]  R. Hegde.  The papillomavirus E2 proteins: structure, function, and biology. , 2002, Annual review of biophysics and biomolecular structure.

[57]  R. Dickerson,et al.  Structure of the B-DNA decamer C-C-A-A-C-G-T-T-G-G and comparison with isomorphous decamers C-C-A-A-G-A-T-T-G-G and C-C-A-G-G-C-C-T-G-G. , 1991, Journal of molecular biology.

[58]  Byung-Kwan Cho,et al.  Genome-wide analysis of Fis binding in Escherichia coli indicates a causative role for A-/AT-tracts. , 2008, Genome research.

[59]  G. Chang,et al.  Crystal Structure of the Lactose Operon Repressor and Its Complexes with DNA and Inducer , 1996, Science.

[60]  Laxmikant V. Kalé,et al.  Scalable molecular dynamics with NAMD , 2005, J. Comput. Chem..

[61]  Atina G. Coté,et al.  Structural basis for recognition of AT-rich DNA by unrelated xenogeneic silencing proteins , 2011, Proceedings of the National Academy of Sciences.

[62]  Robert C. Harris,et al.  Opposites Attract: Shape and Electrostatic Complementarity in Protein-dna Complexes 3.1 Introduction , 2022 .

[63]  P. Nielsen,et al.  A DNA minor groove electronegative potential genome map based on photo-chemical probing , 2011, Nucleic acids research.

[64]  Nicholas M. Luscombe,et al.  Direct and indirect effects of H-NS and Fis on global gene expression control in Escherichia coli , 2010, Nucleic acids research.

[65]  N. Hud,et al.  DNA-cation interactions: The major and minor grooves are flexible ionophores. , 2001, Current opinion in structural biology.

[66]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[67]  B. Halle,et al.  Sequence-specific binding of counterions to B-DNA. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Andrew Travers,et al.  Bacterial chromatin. , 2005, Current opinion in genetics & development.

[69]  A. Joachimiak,et al.  Crystal structure of trp represser/operator complex at atomic resolution , 1988, Nature.

[70]  R. Mann,et al.  Origins of specificity in protein-DNA recognition. , 2010, Annual review of biochemistry.

[71]  G. Koudelka,et al.  P22 c2 repressor-operator complex: mechanisms of direct and indirect readout. , 2008, Biochemistry.

[72]  M Ptashne,et al.  Recognition of a DNA operator by the repressor of phage 434: a view at high resolution , 1988, Science.

[73]  M. Waring,et al.  The use of diaminopurine to investigate structural properties of nucleic acids and molecular recognition between ligands and DNA. , 1998, Nucleic acids research.

[74]  T. D. Schneider,et al.  Information analysis of Fis binding sites. , 1997, Nucleic acids research.

[75]  Randy J. Read,et al.  Phaser crystallographic software , 2007, Journal of applied crystallography.

[76]  V. Zhurkin,et al.  DNA sequence-dependent deformability deduced from protein-DNA crystal complexes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[77]  R. Dickerson,et al.  Intrinsic bending and deformability at the T-A step of CCTTTAAAGG: a comparative analysis of T-A and A-T steps within A-tracts. , 2001, Journal of molecular biology.

[78]  Tamar Schlick,et al.  Innovations in Biomolecular Modeling and Simulations , 2012 .

[79]  Daniel Taylor,et al.  Aknowledgements , 1996, Brain and Development.