Regulation of tryptophan biosynthesis: Trp-ing the TRAP or how Bacillus subtilis reinvented the wheel

The Bacillus subtilis tryptophan biosynthetic genes are regulated by TRAP. Radiographic crystallography indicates that the TRAP complex contains 11 identical subunits arranged in a doughnut-like structure termed the β-wheel. The trpEDCFBA operon is regulated by an attenuation mechanism in which tryptophan-activated TRAP binds to 11 (G/U)AG repeats in the trp leader transcript. TRAP binding blocks formation of an antiterminator structure, thereby promoting the formation of an overlapping terminator, resulting in transcription termination preceding the structural genes. When TRAP is not activated, it is unable to bind to the transcript, which allows anti-terminator formation and, hence, transcription of the operon. TRAP is also responsible for regulating translation of trpE and trpG. TRAP binding to trp operon readthrough transcripts promotes refolding of the RNA such that the trpE Shine-Dalgarno sequence is sequestered in a hairpin, thus inhibiting TrpE synthesis. In the case of trpG, TRAP binds to nine repeats that overlap the ribosome-binding site, thereby blocking translation.