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 Escher ichia coli, BirA, and BCCP, the biotin carboxyl carrier protein to which Bi rA transfers biotin. The model is consistent with prior physical and bioche mical studies. Measurement of transfer rates for variants of BirA with sing le-site mutations in the proposed BirA:BCCP interface region also provides support. The unique feature of the proposed interaction between BirA and BC CP 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. Th e resulting mutually exclusive protein:protein interfaces explain the novel feature of the BirA regulatory system, namely, that transcription of the g enes 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 rol e for the C-terminal domain of BirA that is structurally similar to an SH3 domain.