Structural Constraints on Subunit Assembly

University Of Arizona, Tucson AZ

Investigators

Abstract

0078363 Baldwin, Thomas It is commonly assumed that polypeptides that function as components of multisubunit complexes have the same structure, whether in the complex or as the free subunit. The hypothesis upon which this proposal is based is that this view is not generally accurate. This PI suggest that the conformation of the subunit in the complex may represent only a fraction of the conformations present in an equilibrium population of the free subunits. In support of this hypothesis is the fact that the associate rate constants for assembly of multisubunit complexes span many orders of magnitude in value. Through the experiments described in this proposal, the PI expects to find kinetic heterogeneity in associate rates for the luciferase subunits. Differences in association rates will be evidence for differing structures, and the relative amplitudes of the different rate components will allow quantitative description of the relative populations of conformers. In the second phase of these experiments, the PI will ascertain the extent to which the populations of conformers may be altered by solution conditions and by genetic mutation. A large proportion of all polypeptides in living cells function within multisubunit complexes. The fundamental mechanisms through which these complexes assemble are very poorly understood. There has been extensive work on the energetics of complex formation, but relatively little on the rates of formation and dissociation. Protein-protein interactions play crucial roles in many fundamental life processes. The research of this project is designed to obtain a more detailed and fundamental understanding of the dynamic nature of multisubunit proteins.