Modulation of DNA‐binding specificity within the nuclear receptor family by substitutions at a single amino acid position

作者: Johanna Zilliacus , Anthony P. H. Wright , Jan Carlstedt-Duke , Lennart Nilsson , Jan-Åke Gustafsson

DOI: 10.1002/PROT.340210107

关键词:

摘要: Regulation of gene expression involves a large number transcription factors with unique DNA-binding properties. Many belong to families related proteins that bind similar but distinct sequences. In this study we have analyzed how amino acid substitutions at single position in the domain modulate specificity within nuclear receptor family factors. All possible acids were introduced first DNA recognition helix, and specificities mutants using response elements containing all combinations bases two variable base pair positions. mutant functional binding, could be divided into classes different element specificities. By combining data analysis structural effects mutations by molecular modeling, identify both prohibitive steric interactions as well positive interactions, such hydrogen bonds, function important determinants for specificity. Only residues found naturally glucocorticoid estrogen receptors, glycine glutamate, produce binding The other overlap each somewhat clearly potential contribute diversity family.

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