title: Multiple disordered loops function in corepressor-induced dimerization of the biotin repressor.
abstract: Cooperative association of the Escherichia coli biotin repressor with the biotin operator is allosterically activated by binding of the corepressor, bio-5'-AMP. The corepressor function of the adenylate is due, in part, to its ability to induce repressor dimerization. Since a high-resolution structure of only the apo or unliganded repressor is currently available, the location of the dimerization interface on the protein structure is not known. Here, five mutants in the corepressor-binding domain of the repressor have been analyzed with respect to their DNA-binding and self-assembly properties. Results of these studies reveal that four of the mutant proteins exhibit defects in DNA binding. These same proteins are compromised in self-assembly. Furthermore, in the three-dimensional structure of the apo protein the mutations all lie in partially disordered surface loops, one of which is known to participate directly in corepressor binding. These results suggest that multiple disordered surface loops function in the corepressor-induced dimerization required for sequence-specific DNA binding by the biotin repressor.
authors: Department of Chemistry and Biochemistry, University of Maryland, MD 20742, USA.
authors: K
authors: K
authors: Kwon
authors: E D
authors: ED
authors: Streaker
authors: S
authors: S
authors: Ruparelia
authors: D
authors: D
authors: Beckett
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000378:metabolism*; D000494:Allosteric Regulation; D000495:Allosteric Site; D001059:Apoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001710:Biotin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018983:DNA Footprinting; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D019281:Dimerization; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics*; D029968:Escherichia coli Proteins; D008958:Models, Molecular; D009154:Mutation; D009875:Operator Regions, Genetic / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013816:Thermodynamics; D014157:Transcription Factors
chemical_list: C082099:5'-AMP-biotin; D001059:Apoproteins; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C036824:biotin repressor; D000249:Adenosine Monophosphate; D001710:Biotin; D003850:Deoxyribonuclease I; D019731:Carbon-Nitrogen Ligases; C058125:birA protein, E coli