Comparing the fine specificity of DNA binding by NF-kappaB p50 and p52 using principal coordinates analysis
- 1 March 2003
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 31 (5) , 1497-1501
- https://doi.org/10.1093/nar/gkg231
Abstract
Principal coordinates analysis has been proposed as an efficient way of predicting the binding affinity of a transcription factor to different DNA motifs, as it can model complex interactions that are difficult to represent with standard position-weight matrices. Here we evaluate its ability to distinguish the DNA binding properties of two closely related proteins, the homodimeric forms of NF-kappaB p50 and p52. When tested experimentally against 50 different variants of the generalised NF-kappaB motif GGRRNNYYCC, the binding specificities of p50 and p52 were similar but not identical (correlation rho = 0.86). These experimental data can be modelled accurately with six principal coordinates that are similar for p50 and p52, plus one principal coordinate that is significantly stronger for p52 than for p50, relating to the inner positions of the binding site. These findings are compatible with crystallographic data showing that p52 has greater ability than p50 to form water molecule-mediated hydrogen bonds with inner nucleotide positions of the binding site.Keywords
This publication has 31 references indexed in Scilit:
- Is there a code for protein–DNA recognition? Probab(ilistical)ly…BioEssays, 2002
- Activation by IKKα of a Second, Evolutionary Conserved, NF-κB Signaling PathwayScience, 2001
- TNF-α Induction by LPS Is Regulated Posttranscriptionally via a Tpl2/ERK-Dependent PathwayCell, 2000
- Differential Expression of the Transcription Factor NF-κB during Human Mononuclear Phagocyte Differentiation to Macrophages and Dendritic CellsBiochemical and Biophysical Research Communications, 2000
- How NF-κB is activated: the role of the IκB kinase (IKK) complexOncogene, 1999
- Regulation of DNA binding by Rel/NF-κB transcription factors: structural viewsOncogene, 1999
- Wet and dry interfaces: the role of solvent in protein–protein and protein–DNA recognitionStructure, 1999
- Immunological defects in mice with a targeted disruption in Bcl-3.Genes & Development, 1997
- Abnormal Development of Peripheral Lymphoid Organs in Mice Deficient in LymphotoxinScience, 1994
- Determination of the Nuclear Magnetic Resonance Solution Structure of an Antennapedia Homeodomain-DNA ComplexJournal of Molecular Biology, 1993