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.
Chugh
Jeetender
J
Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
Sharma
Shilpy
S
Hosur
Ramakrishna V
RV
D002850:Chromatography, Gel; D002942:Circular Dichroism; D020558:GTP Phosphohydrolases / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*
D011506:Proteins; D020558:GTP Phosphohydrolases