NMR insights into a megadalton-size protein self-assembly

Protein self-association is critical to many biological functions. However, atomic-level structural characterization of these assemblies has remained elusive. In this report we present insights into the mechanistic details of the process of self-association of the 136- residue GTPase effector domain ( GED) of the endocytic protein dynamin into a megadalton- sized soluble mass. Our approach is based on NMR monitoring of regulated folding and association through Gdn- HCl titration. The results suggest the evolution of a sequence - self- association paradigm. Equally significantly, the study demonstrates an elegant bottom- up strategy that can render large protein self- assemblies accessible to NMR investigations that have remained difficult to date.