Monomer topology defines folding speed of heptamer

Small monomeric proteins often fold in apparent two‐state processes with folding speeds dictated by their native‐state topology. Here we test, for the first time, the influence of monomer topology on the folding speed of an oligomeric protein: the heptameric cochaperonin protein 10 (cpn10), which in the native state has seven β‐barrel subunits noncovalently assembled through β‐strand pairing. Cpn10 is a particularly useful model because equilibrium‐unfolding experiments have revealed that the denatured state in urea is that of a nonnative heptamer. Surprisingly, refolding of the nonnative cpn10 heptamer is a simple two‐state kinetic process with a folding‐rate constant in water (2.1 sec⁻¹; pH 7.0, 20°C) that is in excellent agreement with the prediction based on the native‐state topology of the cpn10 monomer. Thus, the monomers appear to fold as independent units, with a speed that correlates with topology, although the C and N termini are trapped in β‐strand pairing with neighboring subunits. In contrast, refolding of unfolded cpn10 monomers is dominated by a slow association step.