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 beta-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.
Sathyapriya
R
R
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Vijayabaskar
M S
MS
Vishveshwara
Saraswathi
S
D001665:Binding Sites; D019295:Computational Biology; D003196:Computer Graphics; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry; D030561:Databases, Nucleic Acid; D030562:Databases, Protein; D046911:Macromolecular Substances / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D011506:Proteins; D004247:DNA
Biochimie. 2007 Nov;89(11):1291-303
17825469
J Mol Biol. 2005 Feb 4;345(5):1027-45
15644202
EMBO J. 1989 Dec 1;8(12):3825-32
2511003
J Mol Biol. 2004 Mar 19;337(2):285-94
15003447
Structure. 2006 Sep;14(9):1341-2
16962964
J Mol Biol. 1996 Aug 16;261(2):239-54
8757291
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
10592235
Biophys Chem. 2008 May;134(3):111-8
18329160
Biopolymers. 2007 Apr 5-15;85(5-6):456-70
17219397
Cell. 2002 Mar 8;108(5):615-27
11893333
Nucleic Acids Res. 1995 Nov 25;23(22):4707-11
8524664
Biophys J. 2007 May 1;92(9):3052-62
17293401
Nucleic Acids Res. 2003 Dec 15;31(24):7189-98
14654694
Biophys J. 2005 Dec;89(6):4159-70
16150969
J Chem Inf Model. 2006 Jan-Feb;46(1):123-9
16426048
Biophys Chem. 2000 Feb 14;84(1):13-25
10723541
J Mol Biol. 1996 Sep 20;262(2):294-313
8831795
Protein Eng. 2002 Apr;15(4):265-77
11983927
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W124-7
16844974
Nucleic Acids Res. 2001 Jul 1;29(13):2860-74
11433033
J Mol Biol. 1999 Apr 16;287(5):877-96
10222198
J Mol Biol. 1999 Sep 17;292(2):441-64
10493887
Gene. 2005 Dec 30;364:108-13
16249059
Nature. 2001 Feb 1;409(6820):641-5
11214326
Genome Biol. 2000;1(1):REVIEWS001
11104519
Proteins. 2005 Nov 1;61(2):258-71
16121397
J Mol Biol. 2002 Jul 26;320(5):991-1009
12126620
Proc Natl Acad Sci U S A. 2004 May 4;101(18):6864-9
15100411
J Mol Biol. 2003 Dec 5;334(4):781-91
14636602
Biochemistry. 1991 Sep 17;30(37):9060-72
1892819
Structure. 2006 Sep;14(9):1355-67
16962967
Nature. 1997 Sep 18;389(6648):251-60
9305837
Proteins. 1999 Apr 1;35(1):114-31
10090291
Proteins. 2005 Feb 15;58(3):672-82
15617065
Biophys J. 1997 Aug;73(2):640-52
9251783
Curr Opin Struct Biol. 2006 Apr;16(2):213-20
16540311
Trends Cell Biol. 1998 May;8(5):193-7
9695838
Proc Natl Acad Sci U S A. 1997 May 13;94(10):4913-8
9144164
Cell. 1992 Dec 24;71(7):1223-37
1473154
Curr Opin Struct Biol. 1998 Feb;8(1):33-40
9519294