Dynamic properties of the N-terminal swapped dimer of ribonuclease A.

ovine pancreatic RNase (RNase A) forms two 3-dimensional domain-swapped dimers with different quaternary structures. One dimer is characterized by the swapping of the C-terminal region (C-Dimer) and presents a rather loose structure. The other dimer (N-Dimer) exhibits a very compact structure with exchange of the N-terminal helix. Here we report the results of a mol. dynamics/essential dynamics (MD/ED) study carried out on the N-Dimer. This investigation, which represents the first MD/ED anal. on a three-dimensional domain-swapped enzyme, provides information on the dynamic properties of the active site residues as well as on the global motions of the dimer subunits. In particular, the anal. of the flexibility of the active site residues agrees well with recent crystallog. and site-directed mutagenesis studies on monomeric RNase A, thus indicating that domain swapping does not affect the dynamics of the active sites. A slight but significant rearrangement of N-Dimer quaternary structure, favored by the formation of addnl. hydrogen bonds at subunit interface, has been obsd. during the MD simulation. The anal. of collective movements reveals that each subunit of the dimer retains the functional breathing motion obsd. for RNase A. Interestingly, the breathing motion of the two subunits is dynamically coupled, as they open and close in phase. These correlated motions indicate the presence of active site intercommunications in this dimer. On these bases, we propose a speculative mechanism that may explain neg. cooperativity in systems preserving structural symmetry during the allosteric transitions.