The structure of the transition state for folding of domain-swapped dimeric p13suc1.

suc1 has two native states, a monomer and a domain-swapped dimer, in which one molecule exchanges a beta strand with an identical partner. Thus, monomer and dimer have the same structures but are topologically distinct. Importantly, residues that exchange are part of the folding nucleus of the monomer and therefore forming these interactions in the dimer would be expected to incur a large entropic cost. Here we present the transition state for folding/unfolding of domain-swapped dimeric suc1 and compare it with its monomeric counterpart. The same overall structure is observed in the two transition states but the phi values are consistently higher for the domain-swapped dimer. Thus, a greater entropic penalty for bringing together the key interactions in the dimer is overcome by mobilizing more contacts in the transition state, thereby achieving a greater enthalpic gain.