Regulatory Energetics and Protein-DNA Assemblies
Our goal is to understand the fundamental mechanisms of transcriptional regulation at the level of macromolecular structure, function and interactions. Initiation of transcription, the primary point for control of gene expression, is regulated by the spontaneous assembly of regulatory protein and DNA containing complexes. Specific promoters are metabolically or developmentally regulated through coupling interactions between the site-specific protein-DNA interactions and protein-protein interactions, protein and DNA conformational transitions and allosteric transitions mediated by binding of regulatory ligands.
Understanding the chemical basis for these macromolecular interactions provides the foundation to understand biological mechanisms of metabolic regulation, differentiation and development, and carcinogenesis.
Multiple conformations of the cytidine repressor DNA-binding domain coalesce to one upon recognition of a specific DNA surface.
Moody CL, Tretyachenko-Ladokhina V, Laue TM, Senear DF, Cocco MJ.
Biochemistry. 2011 Aug 9;50(31):6622-32. Epub 2011 Jul 18.
An unusual pattern of CytR and CRP binding energetics at Escherichia coli cddP suggests a unique blend of class I and class II mediated activation.
Holt AK, Senear DF.
Biochemistry. 2010 Jan 26;49(3):432-42
Molecular mechanisms of functional rescue mediated by P53 tumor suppressor mutations.
Tan YH, Chen YM, Ye X, Lu Q, Tretyachenko-Ladokhina V, Yang W, Senear DF, Luo R.
Biophys Chem. 2009 Nov;145(1):37-44. Epub 2009 Sep 1.
Pressure dissociation of integration host factor-DNA complexes reveals flexibility-dependent structural variation at the protein-DNA interface.
Senear DF, Tretyachenko-Ladokhina V, Opel ML, Aeling KA, Hatfield GW, Franklin LM, Darlington RC, Alexander Ross JB.
Nucleic Acids Res. 2007;35(6):1761-72. Epub 2007 Feb 25.
DNA deformation energy as an indirect recognition mechanism in protein-DNA interactions.
Aeling KA, Steffen NR, Johnson M, Hatfield GW, Lathrop RH, Senear DF.
IEEE/ACM Trans Comput Biol Bioinform. 2007 Jan-Mar;4(1):117-25.
Indirect recognition in sequence-specific DNA binding by Escherichia coli integration host factor: the role of DNA deformation energy.
Aeling KA, Opel ML, Steffen NR, Tretyachenko-Ladokhina V, Hatfield GW, Lathrop RH, Senear DF.
J Biol Chem. 2006 Dec 22;281(51):39236-48. Epub 2006 Oct 11.
Flexibility and adaptability in binding of E. coli cytidine repressor to different operators suggests a role in differential gene regulation.
Tretyachenko-Ladokhina V, Cocco MJ, Senear DF.
J Mol Biol. 2006 Sep 15;362(2):271-86. Epub 2006 Jul 22.
Tretyachenko-Ladokhina, V, Ross, J.B.A. & Senear, D.F. (2002) "Operator Site Binding by the E. coli CytR Repressor Protein: Different Binding Modes for Different Operators Suggests a Role in Differential Gene Regulation", J. Mol. Biol. 316 (3), 531-546.
Gavigan S.A., Nguyen T., Nguyen N., Senear D.F. (1999) "Role of Multiple CytR Binding Sites on Cooperativity, Competition and Induction at the Escherichia coli udp Promoter" J. Biol Chem 274, 16010-16019.
Rusinova, E., Ross, J.B.A., Laue, T.M., Sowers, L.C. & Rhee, K.Y., Senear, D.F. & Hatfield, G.W. (1998) "Transcriptional Activation by a Ligand-induced Conformational Change in a Protein-DNA Complex" J. Biol. Chem. 273, 11257-11266.
Rusinova, E., Ross, J.B.A., Laue, T.M., Sowers, L.C. & Senear, D.F. (1997) "Linkage Between Operator Binding and Dimer to Octamer Assembly of Bacteriophage Lambda Repressor" Biochemistry 42, 12994-13003
Barbier, C., Short, S & Senear, D.F. (1997) "The Allosteric Mechansim of Induction of CytR Controlled Gene Expression" J. Biol Chem. 272, 16962-16971.
Huang, Y.T. Rusinova, E., Ross, J.B.A. & Senear, D.F. (1997) "An Aromatic Stacking Interaction Between Subunits Helps Mediate DNA Sequence Specificity: Operator Site Discrimination by Phage Lambda cI Repressor ", J. Mol. Biol. 267, 403-417..
The Biophysical Society
The Protein Society
Mechanisms of Gene Expression
Structural Biology and Molecular Biophysics