Competing protein:protein interactions are proposed to control the biological switch of the E coli biotin repressor.
A model is suggested for the complex between the biotin repressor of Escherichia coli, BirA, and BCCP, the biotin carboxyl carrier protein to which BirA transfers biotin. The model is consistent with prior physical and biochemical studies. Measurement of transfer rates for variants of BirA with single-site mutations in the proposed BirA:BCCP interface region also provides support. The unique feature of the proposed interaction between BirA and BCCP is that it uses the same beta-sheet region on the surface of BirA that the protein uses for homodimerization into a form competent to bind DNA. The resulting mutually exclusive protein:protein interfaces explain the novel feature of the BirA regulatory system, namely, that transcription of the genes involved in biotin synthesis is not determined by the level of biotin, per se, but by the level of unmodified BCCP. The model also provides a role for the C-terminal domain of BirA that is structurally similar to an SH3 domain.
Weaver
L H
LH
Institute of Molecular Biology, Howard Hughes Medical Institute, and Department of Physics, University of Oregon, Eugene, Oregon 97403-1229, USA.
Kwon
K
K
Beckett
D
D
Matthews
B W
BW
D000103:Acetyl-CoA Carboxylase / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry*; D001667:Binding, Competitive; D001710:Biotin / Q000096:biosynthesis; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D019281:Dimerization; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins; D054889:Fatty Acid Synthase, Type II; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry*; D014157:Transcription Factors; D018909:src Homology Domains
D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C036824:biotin repressor; D001710:Biotin; D000255:Adenosine Triphosphate; D054889:Fatty Acid Synthase, Type II; D019731:Carbon-Nitrogen Ligases; C058125:birA protein, E coli; D000103:Acetyl-CoA Carboxylase; C079633:biotin carboxyl carrier protein; D008274:Magnesium