Recognition of nucleic acid bases and base-pairs by hydrogen bonding to amino acid side-chains.

Sequence-specific protein-nucleic acid recognition is determined, in part, by hydrogen bonding interactions between amino acid side-chains and nucleotide bases. To examine the repertoire of possible interactions, we have calculated geometrically plausible arrangements in which amino acids hydrogen bond to unpaired bases, such as those found in RNA bulges and loops, or to the 53 possible RNA base-pairs. We find 32 possible interactions that involve two or more hydrogen bonds to the six unpaired bases (including protonated A and C), 17 of which have been observed. We find 186 "spanning" interactions to base-pairs in which the amino acid hydrogen bonds to both bases, in principle allowing particular base-pairs to be selectively targeted, and nine of these have been observed. Four calculated interactions span the Watson-Crick pairs and 15 span the G:U wobble pair, including two interesting arrangements with three hydrogen bonds to the Arg guanidinum group that have not yet been observed. The inherent donor-acceptor arrangements of the bases support many possible interactions to Asn (or Gln) and Ser (or Thr or Tyr), few interactions to Asp (or Glu) even though several already have been observed, and interactions to U (or T) only if the base is in an unpaired context, as also observed in several cases. This study highlights how complementary arrangements of donors and acceptors can contribute to base-specific recognition of RNA, predicts interactions not yet observed, and provides tools to analyze proposed contacts or design novel interactions.

[1]  J. Perona,et al.  Recognition of Flanking DNA Sequences by EcoRV Endonuclease Involves Alternative Patterns of Water-mediated Contacts* , 1998, The Journal of Biological Chemistry.

[2]  François Michel,et al.  The guanosine binding site of the Tetrahymena ribozyme , 1989, Nature.

[3]  R. Roberts,et al.  Hhal methyltransferase flips its target base out of the DNA helix , 1994, Cell.

[4]  Nobutoshi Ito,et al.  Crystal structure at 1.92 Å resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin , 1994, Nature.

[5]  Marc Pignot,et al.  Structure of the N6-adenine DNA methyltransferase M•TaqI in complex with DNA and a cofactor analog , 2001, Nature Structural Biology.

[6]  C. Pabo,et al.  Geometric analysis and comparison of protein-DNA interfaces: why is there no simple code for recognition? , 2000, Journal of molecular biology.

[7]  Roland L. Dunbrack,et al.  Bayesian statistical analysis of protein side‐chain rotamer preferences , 1997, Protein science : a publication of the Protein Society.

[8]  H. Margalit,et al.  Comprehensive analysis of hydrogen bonds in regulatory protein DNA-complexes: in search of common principles. , 1995, Journal of molecular biology.

[9]  A. E. Sauer-Eriksson,et al.  Structure of the SRP19–RNA complex and implications for signal recognition particle assembly , 2002, Nature.

[10]  H. Margalit,et al.  A role for CH...O interactions in protein-DNA recognition. , 1998, Journal of molecular biology.

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

[12]  J. Perona,et al.  Conformational transitions and structural deformability of EcoRV endonuclease revealed by crystallographic analysis. , 1997, Journal of molecular biology.

[13]  G. Varani,et al.  The G x U wobble base pair. A fundamental building block of RNA structure crucial to RNA function in diverse biological systems. , 2000, EMBO reports.

[14]  K S Wilson,et al.  The crystal structure of EcoRV endonuclease and of its complexes with cognate and non‐cognate DNA fragments. , 1993, The EMBO journal.

[15]  M Suzuki,et al.  A framework for the DNA-protein recognition code of the probe helix in transcription factors: the chemical and stereochemical rules. , 1994, Structure.

[16]  M Yarus,et al.  A specific amino acid binding site composed of RNA. , 1988, Science.

[17]  Alan C Cheng,et al.  Structural diversity and isomorphism of hydrogen-bonded base interactions in nucleic acids. , 2003, Journal of molecular biology.

[18]  Susan A. White,et al.  A novel loop-loop recognition motif in the yeast ribosomal protein L30 autoregulatory RNA complex , 1999, Nature Structural Biology.

[19]  E Westhof,et al.  Crystallographic refinement of yeast aspartic acid transfer RNA. , 1985, Journal of molecular biology.

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

[21]  G. Verdine,et al.  Coupling of substrate recognition and catalysis by a human base-excision DNA repair protein. , 2001, Journal of the American Chemical Society.

[22]  L. Kay,et al.  α Helix-RNA Major Groove Recognition in an HIV-1 Rev Peptide-RRE RNA Complex , 1996, Science.

[23]  J. Israelachvili.  Intermolecular and surface forces , 1985 .

[24]  R L Jernigan,et al.  Consistencies of individual DNA base-amino acid interactions in structures and sequences. , 1995, Nucleic acids research.

[25]  R. Chidambaram,et al.  Hydrogen bonding in biological molecules—an update , 1991 .

[26]  A. Krainer,et al.  Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. , 1999, Genes & development.

[27]  M Gerstein,et al.  DNA recognition code of transcription factors. , 1995, Protein engineering.

[28]  A. Frankel,et al.  A novel glutamine-RNA interaction identified by screening libraries in mammalian cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[29]  D. Patel,et al.  Stitching together RNA tertiary architectures. , 1999, Journal of molecular biology.

[30]  A Klug,et al.  Physical basis of a protein-DNA recognition code. , 1997, Current opinion in structural biology.

[31]  HYDROGEN-BOND GEOMETRY IN ORGANIC CRYSTALS , 1985 .

[32]  T. Powers,et al.  Reciprocal stimulation of GTP hydrolysis by two directly interacting GTPases , 1995, Science.

[33]  A. McPherson,et al.  Structure of a ribonuclease B+d(pA)4 complex. , 1996, Acta crystallographica. Section D, Biological crystallography.

[34]  H M Berman,et al.  Protein-DNA interactions: A structural analysis. , 1999, Journal of molecular biology.

[35]  J. Tainer,et al.  Structure of the DNA Repair and Replication Endonuclease and Exonuclease FEN-1 Coupling DNA and PCNA Binding to FEN-1 Activity , 1998, Cell.

[36]  T. Steitz,et al.  Crystal structures of three misacylating mutants of Escherichia coli glutaminyl-tRNA synthetase complexed with tRNA(Gln) and ATP. , 1996, Biochemistry.

[37]  C. Ehresmann,et al.  The Structure of Threonyl-tRNA Synthetase-tRNAThr Complex Enlightens Its Repressor Activity and Reveals an Essential Zinc Ion in the Active Site , 1999, Cell.

[38]  Olga Kennard,et al.  Geometry of the imino-carbonyl (N-H...O:C) hydrogen bond. 1. Lone-pair directionality , 1983 .

[39]  W. Lipscomb,et al.  The crystal structure of Haelll methyltransferase covalently complexed to DNA: An extrahelical cytosine and rearranged base pairing , 1995, Cell.

[40]  S. Jones,et al.  Protein-RNA interactions: a structural analysis. , 2001, Nucleic acids research.

[41]  F. Winkler,et al.  Mg2+ binding to the active site of EcoRV endonuclease: a crystallographic study of complexes with substrate and product DNA at 2 A resolution. , 1995, Biochemistry.

[42]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[43]  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..

[44]  H. Kono,et al.  Structure‐based prediction of DNA target sites by regulatory proteins , 1999, Proteins.

[45]  Philip R. Evans,et al.  Crystal structure of the spliceosomal U2B″–U2A′ protein complex bound to a fragment of U2 small nuclear RNA , 1998, Nature.

[46]  D. Hudson,et al.  RNA recognition by an isolated alpha helix. , 1993, Cell.

[47]  Haruki Nakamura,et al.  Solution structure of a specific DNA complex of the Myb DNA-binding domain with cooperative recognition helices , 1994, Cell.

[48]  Y. Shamoo,et al.  Structure-based analysis of protein-RNA interactions using the program ENTANGLE. , 2001, Journal of molecular biology.

[49]  J. Karn,et al.  Recognition of the high affinity binding site in rev-response element RNA by the human immunodeficiency virus type-1 rev protein. , 1992, Nucleic acids research.

[50]  D. Patel,et al.  Deep penetration of an α-helix into a widened RNA major groove in the HIV-1 rev peptide–RNA aptamer complex , 1996, Nature Structural Biology.

[51]  Wolfram Saenger,et al.  Principles of Nucleic Acid Structure , 1983 .

[52]  D Szwajkajzer,et al.  Molecular and biological constraints on ligand-binding affinity and specificity. , 1997, Biopolymers.

[53]  T. Creighton.  Proteins: Structures and Molecular Properties , 1986 .

[54]  E. Baker,et al.  Hydrogen bonding in globular proteins. , 1984, Progress in biophysics and molecular biology.

[55]  H. Margalit,et al.  Quantitative parameters for amino acid-base interaction: implications for prediction of protein-DNA binding sites. , 1998, Nucleic acids research.

[56]  S. Montaño,et al.  Crystal structures of an N-terminal fragment from Moloney murine leukemia virus reverse transcriptase complexed with nucleic acid: functional implications for template-primer binding to the fingers domain. , 2000, Journal of molecular biology.

[57]  J. Perona,et al.  Role of protein-induced bending in the specificity of DNA recognition: crystal structure of EcoRV endonuclease complexed with d(AAAGAT) + d(ATCTT). , 1998, Journal of molecular biology.

[58]  A. Sentenac,et al.  Specific DNA binding by c-Myb: evidence for a double helix-turn-helix-related motif , 1991, Science.

[59]  B. Ganem.  RNA world , 1987, Nature.

[60]  E Westhof,et al.  Statistical analysis of atomic contacts at RNA–protein interfaces , 2001, Journal of molecular recognition : JMR.

[61]  P. Gollnick,et al.  Probing the TRAP-RNA interaction with nucleoside analogs. , 1999, RNA.

[62]  B. Roques,et al.  Structure of the complex between the HIV-1 nucleocapsid protein NCp7 and the single-stranded pentanucleotide d(ACGCC). , 1998, Journal of molecular biology.

[63]  E Westhof,et al.  On the wobble GoU and related pairs. , 2000, RNA.

[64]  D. Draper.  Themes in RNA-protein recognition. , 1999, Journal of molecular biology.

[65]  M. Horvath,et al.  Crystal Structure of the Oxytricha nova Telomere End Binding Protein Complexed with Single Strand DNA , 1998, Cell.

[66]  Olga Kennard,et al.  Geometry of the imino-carbonyl (N-H...O:C) hydrogen bond. 1. Lone-pair directionality , 1983 .

[67]  R. B. Greaves,et al.  Structure of the trp RNA-binding attenuation protein, TRAP, bound to RNA , 1999, Nature.