Structural basis of nearest-neighbor cooperativity in the ring-shaped gene regulatory protein TRAP from protein engineering and cryo-EM.

The homo-dodecameric ring-shaped RNA binding attenuation protein (TRAP) from binds up to twelve tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5' leader region of the operon mRNA, thereby downregulating biosynthesis of Trp. Thermodynamic measurements of Trp binding have revealed a range of cooperative behavior for different TRAP variants, even if the averaged apparent affinities for Trp have been found to be similar. Proximity between the ligand binding sites, and the ligand-coupled disorder-to-order transition has implicated nearest-neighbor interactions in cooperativity.

Solution structure, dynamics and tetrahedral assembly of Anti-TRAP, a homo-trimeric triskelion-shaped regulator of tryptophan biosynthesis in .

Cellular production of tryptophan is metabolically expensive and tightly regulated. The small zinc binding Anti-TRAP protein (AT), which is the product of the gene, is upregulated in response to accumulating levels of uncharged tRNA through a T-box antitermination mechanism. AT binds to the undecameric axially symmetric ring-shaped protein TRAP ( RNA Binding Attenuation Protein), thereby preventing it from binding to the leader RNA.

Structural basis of nearest-neighbor cooperativity in the ring-shaped gene regulatory protein TRAP from protein engineering and cryo-EM.

Homotropic cooperativity is widespread in biological regulation. The homo-oligomeric ring-shaped RNA binding attenuation protein (TRAP) from bacillus binds multiple tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5' leader region of the operon mRNA. Ligand-activated binding to this specific RNA sequence regulates downstream biosynthesis of Trp in a feedback loop.

Solution structure, dynamics and tetrahedral assembly of Anti-TRAP, a homo-trimeric triskelion-shaped regulator of tryptophan biosynthesis in .

Cellular production of tryptophan is metabolically expensive and tightly regulated. The small zinc binding Anti-TRAP protein (AT), which is the product of the gene, is upregulated in response to accumulating levels of uncharged tRNA through a T-box antitermination mechanism. AT binds to the undecameric ring-shaped protein TRAP ( RNA Binding Attenuation Protein), thereby preventing it from binding to the leader RNA.

Thermodynamic coupling between neighboring binding sites in homo-oligomeric ligand sensing proteins from mass resolved ligand-dependent population distributions.

Homo-oligomeric ligand-activated proteins are ubiquitous in biology. The functions of such molecules are commonly regulated by allosteric coupling between ligand-binding sites. Understanding the basis for this regulation requires both quantifying the free energy ΔG transduced between sites, and the structural basis by which it is transduced.