A Simulation Based Analysis of the Oligomeric Plasticity of Sm Protein Assemblies

Abstract

RNA-associated Sm proteins can be found in all three domains of life. In eukarya, Sm proteins are well-studied in connection with their roles mRNA splicing. In bacteria, the Sm protein Hfq acts as an RNA chaperone, playing vital roles in mRNA-sRNA annealing and RNA-based regulatory networks. In archaea, the functional roles of Sm proteins remains an open question. Sm proteins assemble into cyclic oligomers of 5, 6, 7, or 8 subunits, and the assemblies can be either homo- or heteromeric. Bacterial Sm proteins have only been found as homo-hexamers, while eukaryotic Sm proteins typically assemble into hetero-heptamers. Archaeal Sm proteins have been found as homomeric hexamers, heptamers, and octamers. Despite this variation in quaternary structure, all Sm monomers exhibit nearly identical tertiary structures. How can this be? What is the origin of this oligomeric plasticity, if not encoded in the monomer? We have used a systematic array of molecular dynamics simulations to examine the interfaces between Sm subunits, and have developed several quantitative relations that link the results of dimer simulations to the behavior of complete rings. The simulations reveal that Sm oligomers are remarkably flexible. Sm dimers can adopt multiple conformations, and Sm rings are distinctly asymmetric. In particular, the octameric ring of an Sm-like archaeal protein deforms drastically, and dimers of that protein appear to adopt a non-Sm-like tertiary structure. For a dimer of the E. coli Sm protein, our simulations show one monomer twisting nearly fifteen degrees from its position in the crystal structure. The surprising flexibility of Sm oligomers may be related to the dynamical effects of RNA binding and we are currently investigating these effects in a variety of Sm systems.