On 12.12.2014 23:53, [email protected] wrote:
When you state however that it is highly unlikely for a homo-oligomer to show asymmetry, I think you are forgetting the well-known phenomenon of half-of-sites reactivity among enzymes. A simple internet search will in fact show many examples where two copies of the same molecule form a complex, adopting different conformations to do so. Symmetry-breaking is a general feature of Nature, so it is not too surprising that proteins may adapt to a partner's presence in this way.
One has to be careful with what we mean with the word "asymmetry". Monod's reasoning simply says that a single molecule can't associate in a heterologous way unless the open binding surfaces are closed by symmetry. Thus it precludes asymmetry in the sense of the quaternary structure assembly of homomers, it does not say however that the subunits of a homomer can't have slight conformational differences. The quaternary structure is still symmetric (not in the strict crystallographic sense of perfect mathematical symmetry, but in the sense of approximate symmetry resulting in superpositions with low rmsds).
The most important concept here is that the binding interfaces MUST be symmetric due to topological reasons: either in the isologous sense (2-fold symmetry, face-to-face binding) or in the heterologous sense (cyclic symmetry where the molecules associate in a face-to-back fashion, where both the face and back sites are satisfied simultaneously in every molecule in the assembly). Levy and Teichmann have a very nice review on this: http://www.sciencedirect.com/science/article/pii/B9780123869319000027
In any case the half-of-sites reactivity phenomenon is of course perfectly possible, there's nothing in the MWC paper against that idea.
The main point I was trying to make is: if a crystal is composed of only one type of protein molecule (no ligands or extra molecules around) one should not conclude that it assembles in an asymmetric way through open heterologous interfaces. If there's no other molecules around to produce the asymmetry, then what you see in the crystal is a bunch of crystal contacts.
Jose
