On 12.12.2014 23:53, [log in to unmask] 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
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