Visualization of Chaperone Mediated Protein Folding Using X-ray Crystallography

Abstract

How chaperones affect the structure of their substrate proteins is a central question in chaperone biology. There have been some successes in using crystallography to elucidate chaperone complexes. However, given the heterogenous and at least partially disordered nature of chaperone–substrate interactions, this question has often proven to be very difficult to address using conventional crystallographic approaches. While a few chaperone–client structures have been solved, those solved at high resolution often involve short peptides or fully folded proteins serving as substrates, both of which may not adequately reflect the physiological nature of chaperone substrates. Recently a crystallographic approach using heavy atom derivatives has allowed the tracking of multiple conformations of substrates bound to a chaperone. This chapter tracks the successes and challenges of crystallography on chaperone:substrate complexes and comments on the suitability of the approach in the future.