Insights into Protein–DNA Interactions through Structure Network Analysis

Protein–DNA interactions are crucial for many cellular processes. Now with the increased availability of structures of protein–DNA complexes, gaining deeper insights into the nature of protein–DNA interactions has become possible. Earlier, investigations have characterized the interface properties by considering pairwise interactions. However, the information communicated along the interfaces is rarely a pairwise phenomenon, and we feel that a global picture can be obtained by considering a protein–DNA complex as a network of noncovalently interacting systems. Furthermore, most of the earlier investigations have been carried out from the protein point of view (protein-centric), and the present network approach aims to combine both the protein-centric and the DNA-centric points of view. Part of the study involves the development of methodology to investigate protein–DNA graphs/networks with the development of key parameters. A network representation provides a holistic view of the interacting surface and has been reported here for the first time. The second part of the study involves the analyses of these graphs in terms of clusters of interacting residues and the identification of highly connected residues (hubs) along the protein–DNA interface. A predominance of deoxyribose–amino acid clusters in β-sheet proteins, distinction of the interface clusters in helix–turn–helix, and the zipper-type proteins would not have been possible by conventional pairwise interaction analysis. Additionally, we propose a potential classification scheme for a set of protein–DNA complexes on the basis of the protein–DNA interface clusters. This provides a general idea of how the proteins interact with the different components of DNA in different complexes. Thus, we believe that the present graph-based method provides a deeper insight into the analysis of the protein–DNA recognition mechanisms by throwing more light on the nature and the specificity of these interactions.

[1]  S Parodi,et al.  Thermodynamics of condensation of nuclear chromatin. A differential scanning calorimetry study of the salt-dependent structural transitions. , 1991, Biochemistry.

[2]  Ponraj Prabakaran,et al.  Classification of protein-DNA complexes based on structural descriptors. , 2006, Structure.

[3]  Janet M Thornton,et al.  Protein-DNA interactions: amino acid conservation and the effects of mutations on binding specificity. , 2002, Journal of molecular biology.

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

[5]  Shandar Ahmad,et al.  ReadOut: structure-based calculation of direct and indirect readout energies and specificities for protein–DNA recognition , 2006, Nucleic Acids Res..

[6]  A. Papavassiliou,et al.  Hydrogen bonds in protein-DNA complexes: where geometry meets plasticity. , 2007, Biochimie.

[7]  S. Vishveshwara,et al.  Identification of side-chain clusters in protein structures by a graph spectral method. , 1999, Journal of molecular biology.

[8]  A. Atilgan,et al.  Screened nonbonded interactions in native proteins manipulate optimal paths for robust residue communication. , 2006, Biophysical journal.

[9]  Shan Chang,et al.  Amino acid network and its scoring application in protein-protein docking. , 2008, Biophysical chemistry.

[10]  Saraswathi Vishveshwara,et al.  Correlation of the Side-Chain Hubs with the Functional Residues in DNA Binding Protein Structures , 2006, J. Chem. Inf. Model..

[11]  Winship Herr,et al.  A Regulated Two-Step Mechanism of TBP Binding to DNA A Solvent-Exposed Surface of TBP Inhibits TATA Box Recognition , 2002, Cell.

[12]  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.

[13]  T. Richmond,et al.  DNA binding within the nucleosome core. , 1998, Current opinion in structural biology.

[14]  N. Kannan,et al.  Analysis of homodimeric protein interfaces by graph-spectral methods. , 2002, Protein engineering.

[15]  D. Lejeune,et al.  Protein–nucleic acid recognition: Statistical analysis of atomic interactions and influence of DNA structure , 2005, Proteins.

[16]  Samuel Selvaraj,et al.  Role of inter and intramolecular interactions in protein-DNA recognition. , 2005, Gene.

[17]  M. Rooman,et al.  Structural classification of HTH DNA-binding domains and protein-DNA interaction modes. , 1996, Journal of molecular biology.

[18]  Taner Z Sen,et al.  A DNA-centric look at protein-DNA complexes. , 2006, Structure.

[19]  Antonina Silkov,et al.  Structural alignment of protein--DNA interfaces: insights into the determinants of binding specificity. , 2005, Journal of molecular biology.

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

[21]  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..

[22]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[23]  Clifford Stein,et al.  Introduction to Algorithms, 2nd edition. , 2001 .

[24]  R. Müller,et al.  Asymmetrical recognition of the palindromic AP1 binding site (TRE) by Fos protein complexes. , 1989, The EMBO journal.

[25]  R. Dickerson,et al.  How proteins recognize the TATA box. , 1996, Journal of molecular biology.

[26]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[27]  H Weinstein,et al.  Does TATA matter? A structural exploration of the selectivity determinants in its complexes with TATA box-binding protein. , 1997, Biophysical journal.

[28]  M. Karplus,et al.  Three key residues form a critical contact network in a protein folding transition state , 2001, Nature.

[29]  Samuel Selvaraj,et al.  Intermolecular and intramolecular readout mechanisms in protein-DNA recognition. , 2004, Journal of molecular biology.

[30]  G. Grant,et al.  Role of aromatic amino acids in protein-nucleic acid recognition. , 2007, Biopolymers.

[31]  S Vishveshwara,et al.  Backbone cluster identification in proteins by a graph theoretical method. , 2000, Biophysical chemistry.

[32]  D. Sterner,et al.  The SAGA unfolds: convergence of transcription regulators in chromatin-modifying complexes. , 1998, Trends in cell biology.

[33]  T. Kerppola,et al.  Structural basis of DNA bending and oriented heterodimer binding by the basic leucine zipper domains of Fos and Jun. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[34]  A. del Sol,et al.  Small‐world network approach to identify key residues in protein–protein interaction , 2004, Proteins.

[35]  Janet M Thornton,et al.  Using electrostatic potentials to predict DNA-binding sites on DNA-binding proteins. , 2003, Nucleic acids research.

[36]  C. Woodcock,et al.  Chromatin architecture. , 2006, Current opinion in structural biology.

[37]  Karolin Luger,et al.  Molecular recognition of the nucleosomal "supergroove". , 2004, Proceedings of the National Academy of Sciences of the United States of America.

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

[39]  Victoria A. Higman,et al.  Uncovering network systems within protein structures. , 2003, Journal of molecular biology.

[40]  J. Thornton,et al.  An overview of the structures of protein-DNA complexes , 2000, Genome Biology.

[41]  S. Vishveshwara,et al.  A network representation of protein structures: implications for protein stability. , 2005, Biophysical journal.