A framework for the DNA-protein recognition code of the probe helix in transcription factors: the chemical and stereochemical rules.

BACKGROUND Understanding the general mechanisms of sequence specific DNA recognition by proteins is a major challenge in structural biology. The existence of a 'DNA recognition code' for proteins, by which certain amino acid residues on a protein surface confer specificity for certain DNA bases, has been the subject of much discussion. However, no simple code has yet been established. RESULTS The principles of DNA recognition can be described at two levels. The 'chemical' rules describe the partnerships between amino acid side chains and DNA bases making favourable interactions in the major groove of DNA. Here I analyze the occurrence of nucleotide-amino acid contacts in previously determined crystal structures of DNA-protein complexes and find that simple rules pertain. I also describe 'stereochemical' rules for the probe helix type of DNA-binding motif found in certain transcription factors including leucine zipper and homeodomain proteins. These are a consequence of the binding geometry, and specify the amino acid and base positions used for the contacts, and the sizes of residues in the contact interface. CONCLUSIONS The chemical rules can be generalized for any DNA-binding motif, while the stereochemical rules are specific to a particular DNA-binding motif. The recognition code for a particular binding motif can be described by combining the two sets of rules.

[1]  K. Struhl,et al.  The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted α Helices: Crystal structure of the protein-DNA complex , 1992, Cell.

[2]  S. Grossman,et al.  Crystal structure at 1.7 Å of the bovine papillomavirus-1 E2 DMA-binding domain bound to its DNA target , 1992, Nature.

[3]  T. Steitz,et al.  Crystal structure of a CAP-DNA complex: the DNA is bent by 90 degrees , 1991, Science.

[4]  S. Burley,et al.  Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5 , 1993, Nature.

[5]  R. Brent,et al.  A genetic model for interaction of the homeodomain recognition helix with DNA. , 1991, Science.

[6]  N. Pavletich,et al.  Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A , 1991, Science.

[7]  B. Müller-Hill,et al.  Identification of three residues in the basic regions of the bZIP proteins GCN4, C/EBP and TAF‐1 that are involved in specific DNA binding. , 1993, The EMBO journal.

[8]  C. Chothia.  Principles that determine the structure of proteins. , 1984, Annual review of biochemistry.

[9]  R. Sauer,et al.  Protein-DNA recognition. , 1984, Annual review of biochemistry.

[10]  R. Sauer.  Protein-DNA interactions , 1991 .

[11]  Norbert Perrimon,et al.  The orthodenticle gene is regulated by bicoid and torso and specifies Drosophila head development , 1990, Nature.

[12]  Fritz Eckstein,et al.  Nucleic acids and molecular biology , 1987 .

[13]  J M Rosenberg,et al.  Structure of the DNA-Eco RI endonuclease recognition complex at 3 A resolution. , 1986, Science.

[14]  T. Richmond,et al.  The X-ray structure of the GCN4-bZIP bound to ATF/CREB site DNA shows the complex depends on DNA flexibility. , 1993, Journal of molecular biology.

[15]  R. Klevit,et al.  Recognition of DNA by Cys2,His2 zinc fingers , 1991, Science.

[16]  Cynthia Wolberger,et al.  Crystal structure of a MAT alpha 2 homeodomain-operator complex suggests a general model for homeodomain-DNA interactions. , 1991, Cell.

[17]  Pierre Gönczy,et al.  A single amino acid can determine the DNA binding specificity of homeodomain proteins , 1989, Cell.

[18]  K. Yamamoto,et al.  Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA , 2003, Nature.

[19]  J R Desjarlais,et al.  Use of a zinc-finger consensus sequence framework and specificity rules to design specific DNA binding proteins. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Sauer,et al.  The Basic-Region Leucine-Zipper Family of DNA Binding Proteins , 1992 .

[21]  Wolfgang Driever,et al.  The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo , 1989, Nature.

[22]  C. Desplan,et al.  The homeodomain: A new face for the helix‐turn‐helix? , 1992, BioEssays : news and reviews in molecular, cellular and developmental biology.

[23]  R. Bryan,et al.  The crystal structure of EcoRV endonuclease and of its complexes with cognate and non-cognate DNA fragments. , 1993 .

[24]  C. Pabo,et al.  Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers. , 1993, Science.

[25]  J M Rosenberg,et al.  Refinement of Eco RI endonuclease crystal structure: a revised protein chain tracing. , 1990, Science.

[26]  Alfonso Mondragón,et al.  The phage 434 Cro/OR1 complex at 2.5 A resolution. , 1991, Journal of molecular biology.

[27]  R. Sauer,et al.  Transcription factors: structural families and principles of DNA recognition. , 1992, Annual review of biochemistry.

[28]  S. Harrison,et al.  Conserved residues make similar contacts in two repressor-operator complexes. , 1990, Science.

[29]  Brian W. Matthews,et al.  No code for recognition , 1988, Nature.

[30]  R. Brennan.  Interactions of the helix-turn-helix binding domain , 1991 .

[31]  S. Harrison,et al.  Structure of a phage 434 Cro/DNA complex , 1988, Nature.

[32]  John W. R. Schwabe,et al.  The crystal structure of a two zinc-finger peptide reveals an extension to the rules for zinc-finger/DNA recognition , 1993, Nature.

[33]  S. Harrison,et al.  Structure of the represser–operator complex of bacteriophage 434 , 1987, Nature.

[34]  John W. R. Schwabe,et al.  The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: How receptors discriminate between their response elements , 1993, Cell.

[35]  B. Müller-Hill,et al.  Rules for Protein DNA Recognition for a Family of Helix-Turn-Helix Proteins , 1991 .

[36]  Jordan,et al.  Structure of the lambda complex at 2.5 A resolution: details of the repressor-operator interactions , 1988, Science.

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

[38]  B. Müller-Hill,et al.  The DNA binding specificity of the basic region of the yeast transcriptional activator GCN4 can be changed by substitution of a single amino acid. , 1993, Nucleic acids research.

[39]  Stephen K. Burley,et al.  Recognition by Max of its cognate DNA through a dimeric b/HLH/Z domain , 1993, Nature.

[40]  S. Phillips,et al.  Crystal structure of the met represser–operator complex at 2.8 Å resolution reveals DNA recognition by β-strands , 1992, Nature.

[41]  M. Suzuki.  Common features in DNA recognition helices of eukaryotic transcription factors. , 1993, The EMBO journal.

[42]  C. Lawson,et al.  Tandem binding in crystals of a trp represser/operator half-site complex , 1993, Nature.

[43]  Carl O. Pabo,et al.  Crystal structure of an engrailed homeodomain-DNA complex at 2.8 Å resolution: A framework for understanding homeodomain-DNA interactions , 1990, Cell.

[44]  B. Müller-Hill,et al.  A model of the lac repressor-operator complex based on physical and genetic data. , 1991, European journal of biochemistry.

[45]  G. Marzluf,et al.  Mutational analysis of the DNA-binding domain of the CYS3 regulatory protein of Neurospora crassa , 1991, Molecular and cellular biology.

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

[47]  Michael Carey,et al.  DNA recognition by GAL4: structure of a protein-DNA complex , 1992, Nature.

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