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CCP4BB  December 2014

CCP4BB December 2014

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Subject:

Re: asymmetric homotrimer in the asu

From:

Jose Manuel Duarte <[log in to unmask]>

Reply-To:

Jose Manuel Duarte <[log in to unmask]>

Date:

Sat, 13 Dec 2014 12:12:30 +0100

Content-Type:

text/plain

Parts/Attachments:

Parts/Attachments

text/plain (41 lines)

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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