Fig. 1.
Allostery and protein plasticity in one-component systems. a Schematic drawing of one-component signal transduction systems in bacterial cells. The signal (yellow sphere) is sensed by the ligand-binding domain (LBD) via association into the allosteric site. This results in conformational rearrangements at the distant orthosteric site, in this case located at an output DNA-binding domain (DBD). Allosteric coupling pathways are depicted as red arrows, effecting the transition from an “inactive” apo protein (left) towards an “activated” holo-protein (right). Created with BioRender.com b illustration of a two-state switching allosteric mechanism, engaging rigid-body motions. Cartoon representations of the crystal structures of apo (PDB ID 4RAY) and metal-bound holo (PDB 4RB1) Fur MSR-1 from Magnetospirillum gryphiswaldense. The holo form exhibits in this case bound Mn2+ cations and was solved in complex with its cognate DNA Fur-box. Each monomer in the dimer is distinguished with tones of gray and domain labels with a prime symbol. Only one DNA-binding domain (DBD) is colored with a blue-to-red ramp from N-to-C-terminus, so that the rigid-body rotation is clearer comparing the apo to the holo form. Allosterically induced rotations of ca. 180° are observed on both DBDs as indicated, bringing their conformation into DNA-binding-competent geometry (Deng et al. 2015). c Allosteric transitions can implicate high protein dynamics with side/main chain flexibility in one-component systems. Cartoon representations of the crystal structures of FasR, a TetR-like transcription factor from M. tuberculosis. The allosteric effect of long-chain fatty acids that bind within the LBD (leftmost panel, PDB 6O6N) rigidifies an otherwise flexible apo form (mid panel,
adapted from PDB 6O6O) by completing a hydrophobic spine and rendering a DNA-binding-incompetent geometry. 6O6O is here schematically blurred to highlight regions of higher flexibility in TFRs, constituting a multi-state conformational ensemble. DNA selects the proper conformation and stabilizes the DNA-bound form (rightmost panel, PDB 6O6N), achieving the proper distance between DBD helices that insert into the major groove (Lara et al. 2020)