AUTHOR=Strawn Rebecca , Murthy Parvathi S. , Ettrich Rüdiger H. , Pelczer István , Carey Jannette 

TITLE=Symmetry of a partially-ligated state maintained by dynamics in a negatively cooperative system

JOURNAL=Frontiers in Biophysics

VOLUME=Volume 2 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/biophysics/articles/10.3389/frbis.2024.1359979

DOI=10.3389/frbis.2024.1359979

ISSN=2813-7183

ABSTRACT=Symmetry was a key concept underlying the MWC model for allostery advanced in 1965 by Monod, Wyman, and Changeux. The reciprocal interactions of symmetrically-arranged identical subunits were proposed to stabilize multimeric assemblies together with the free energy from bound ligands that progressively favor a monomer-like state. Structural symmetry of subunits was assumed to be maintained in the partially-ligated states, even if ligand placement itself is not symmetric. Partially-ligated states can be populated sufficiently for experimental study only in negatively cooperative systems, which were not considered in the MWC model. The work reported here uses 1 H, 13 C, 15 N, and 19 F NMR to evaluate the structural symmetry of the hexameric arginine repressor of E. coli, a negatively cooperative system, with a single bound L-arginine ligand. The analysis indicates that the singly-ligated hexamer maintains structural symmetry as probed by these four NMR nuclei. The results are consistent with earlier molecular dynamics simulations suggesting that the global dynamics of the singly-ligated assembly are harnessed to maintain structural symmetry. The results extend MWC symmetry concepts to this negatively cooperative system, and indicate a role for global dynamics in allostery.