Cooperativity in λ Repressor

Source: Stayrook et al. (2008). Crystal structure of the λ repressor and a model for pairwise cooperative operator binding. Nature 452:1022-1025.

My first reaction after seeing paper was, "THEY'RE STILL WORKING ON λ". Well, apparently they do and they have some paradigm shifting results. λ (cI) is the key trasncription factor for lysogeny in this bacteriophage. Simultanuous repression and activation of two distinct (and adjacent) promoters by 'alternate pairwise' binding of this protein is the key to the bistability of the lytic-lysogeny dicotomy. For background information, I refer you to wikipedia. The key question that the authors need to answer is the 'alternate pairwise' binding, where a pair of cI dimers can either take on OR1-OR2 or OR2-OR3 (if OR1 is mutated). Our structural knowledge of cI doesn't tell us why there is no OR1-OR2-OR3 trimer. This exactly what the authors explain through solving the structure of λ repressor in its complete dimer structure. Apparently, the inherent symmetry that we have in mind does not exist (see below; left: schematic cI structure, right: what it really looks like).

This assymetry impedes a third cI dimer from both binding the other cIs and DNA at the same time.