Type II chaperonns, prefoldin, and the tubulin-specific chaperones

This chapter describes several experiments that give a qualitative feel for how Type II chaperonins might facilitate protein folding. Imaging of CCT/actin complexes and experiments on actin and tubulin folding in vitro suggest that target proteins bind to chaperonin in a surprisingly native-like state, probably consisting of only one or a few kinetically trapped folding intermediates. Chaperonins are a specialized but ubiquitous group of molecular chaperones that are characterized by a multisubunit ring structure. Chaperonins exist in all kingdoms of life, in all cases using cycles of ATP binding and hydrolysis to generate allosteric changes that promote the correct folding of bound target protein. Type I chaperonins are present in prokaryotes (exemplified by GroEL/GroES), in mitochondria (exemplified by Hsp60/hspl0), and in chloroplasts (exemplified by Rubisco subunit binding protein), while Type II chaperonins include the chaperonin present in archaea (exemplified by the thermosome) and the chaperonin present in the cytosol of eukaryotes (referred to here as CCT, for cytosolic chaperonin-containing TCP-1, but which is also termed c-cpn or TriC). Indeed, chaperones in general appear to function by releasing and rebinding target proteins, allowing a kinetic partition of folding intermediates among the chaperone proteins present in the cell, and leading to their folding, subcellular sorting, or degradation.