The protein folding problem is a fundamental question in molecular biology. We have initiated studies to examine the pathway of protein folding as it occurs in vitro and in vivo . Protein folding, in vitro , can occur without the aid of additional factors, demonstrating that the amino-acid sequence contains the full information required to specify the native conformation. We have been examining models systems for studying the structure of possible folding intermediates using small-angle scattering, ultraviolet circular dichroism and nuclear magnetic resonance spectroscopy. These studies may aid in understanding the pathway of protein folding.
Recent evidence indicates that the in vivo folding process requires so-called molecular chaperones.
These proteins interact with many unfolded or partially unfolded intermediates apparently without specific recognition of defined sequence motifs. We are interested in characterizing the interactions between molecular chaperones and their substrate proteins, as well as the functional complexes formed between individual chaperone proteins. Three dimensional representations of two ClpP heptameric rings . Sequence conservation in the Clp protease family is illustrated by the black colored residues in three subunits. Medline Abstract Wang, J., Hartling, J.A., and Flanagan, J.M. Crystal structure determination of Escherichia coli ClpP starting from an EM-derived mask.