Protein oligomerization in the cell has important implications in both health and disease and an understanding of the mechanisms by which proteins can self-associate is, therefore, of critical interest. Initial stages of the oligomerization process can be hard to detect, as they often involve the formation of sparsely populated and transient states that are difficult to characterize by standard biophysical approaches. Using relaxation dispersion NMR spectroscopy we study the oligomerization of human profilin-1, a protein that regulates the polymerization of actin. We show that in solution and at millimolar concentrations profilin-1 is predominantly monomeric. However, fits of concentration dependent relaxation ... More
Protein oligomerization in the cell has important implications in both health and disease and an understanding of the mechanisms by which proteins can self-associate is, therefore, of critical interest. Initial stages of the oligomerization process can be hard to detect, as they often involve the formation of sparsely populated and transient states that are difficult to characterize by standard biophysical approaches. Using relaxation dispersion NMR spectroscopy we study the oligomerization of human profilin-1, a protein that regulates the polymerization of actin. We show that in solution and at millimolar concentrations profilin-1 is predominantly monomeric. However, fits of concentration dependent relaxation data are consistent with the formation of a higher order oligomer that is generated via a multi-step process. Together with crystallographic data on profilin-2, a homologue of the protein studied here, our results suggest that profilin-1 forms a sparsely populated tetrameric conformer in solution.
