Comparing the fine specificity of DNA binding by NF-kappaB p50 and p52 using principal coordinates analysis.
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.
Nijnik
Anastasia
A
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Mott
Richard
R
Kwiatkowski
Dominic P
DP
Udalova
Irina A
IA
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D004247:DNA / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D016015:Logistic Models; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009841:Oligonucleotides; D021122:Protein Subunits; D004247:DNA