Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs.
Coactivator recruitment by activation function 2 (AF2) in the steroid receptor ligand binding domain takes place through binding of an LXXLL amphipathic alpha-helical motif at the AF2 hydrophobic surface. The androgen receptor (AR) and certain AR coregulators are distinguished by an FXXLF motif that interacts selectively with the AR AF2 ... site. Here we show that LXXLL and FXXLF motif interactions with steroid receptors are modulated by oppositely charged residues flanking the motifs and charge clusters bordering AF2 in the ligand binding domain. An increased number of charged residues flanking AF2 in the ligand binding domain complement the two previously characterized charge clamp residues in coactivator recruitment. The data suggest a model whereby coactivator recruitment to the receptor AF2 surface is initiated by complementary charge interactions that reflect a reversal of the acidic activation domain-coactivator interaction model.
Mesh Terms:
Acetyltransferases, Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, COS Cells, Carcinoma, Hepatocellular, Cercopithecus aethiops, Histone Acetyltransferases, Humans, Ligands, Liver Neoplasms, Models, Molecular, Molecular Sequence Data, Nuclear Receptor Coactivator 1, Nuclear Receptor Coactivator 2, Nuclear Receptor Coactivator 3, Oncogene Proteins, Peptide Fragments, Protein Binding, Protein Conformation, Protein Interaction Mapping, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, Androgen, Receptors, Steroid, Recombinant Fusion Proteins, Static Electricity, Structure-Activity Relationship, Trans-Activators, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured, Two-Hybrid System Techniques
Acetyltransferases, Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, COS Cells, Carcinoma, Hepatocellular, Cercopithecus aethiops, Histone Acetyltransferases, Humans, Ligands, Liver Neoplasms, Models, Molecular, Molecular Sequence Data, Nuclear Receptor Coactivator 1, Nuclear Receptor Coactivator 2, Nuclear Receptor Coactivator 3, Oncogene Proteins, Peptide Fragments, Protein Binding, Protein Conformation, Protein Interaction Mapping, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, Androgen, Receptors, Steroid, Recombinant Fusion Proteins, Static Electricity, Structure-Activity Relationship, Trans-Activators, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured, Two-Hybrid System Techniques
Mol. Cell. Biol.
Date: Mar. 01, 2003
PubMed ID: 12612084
View in: Pubmed Google Scholar
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