By integrating kinetic with structural studies, we recently elucidated how heterohexameric co-chaperonin (90 kDa) inhibits the formation of islet amyloid polypeptide fibrils associated with diabetes. Our methyl NMR approach can also be used to study large chaperone in the heat of the action, while they are processing their client proteins. This strategy can be applied to very molecular machine, such as chaperonin powered by ATP hydrolysis, with a molecular weight as high as 1 MDa. We are currently applying this approach to study the mechanism of the ClpP/ClpX complex, a proteolytic machinery of 800 kDa containing 26 subunits.
Key Publications
"Structural Investigation of a Chaperonin in Action Reveals How Nucleotide Binding Regulates the Functional Cycle" Science Advances
"The role of heat shock proteins in preventing amyloid toxicity" Frontiers Molecular Biosciences
"Structural Basis for the Inhibition of IAPP Fibril Formation by the Co-Chaperonin Prefoldin" Nature Communications