Hi,
In many X-ray structures, including this of the apo PPARγ, the receptor was solved in a homodimer in which the chain B showed helix 12 in an "open" conformation whereas the chain A was almost identical to agonist one. It seems that there is some discussion and/or misunderstanding of the experimental data and two completely controversial hypothesis were adopted by different scientific groups. One of the commonly adopted explanation is that the distorted H12 in one of the monomers is due to crystallographic contacts in a consistent with many previously published PPARγ structures. Despite that in many other papers, including reviews, it has been suggested that agonist H12 state, present in chain A, might be due to crystallographic artifact in which low affinity ligands were bound and not modeled, or in which crystallization was attained for the less mobile conformer, thus forcing the C-terminal helix to pack. It has been even also suggested that the positioning of the lipid ligand and the stabilization of helix 12 are coupled processes. However, there are many X-ray structures, as such for example pdb id 2q5p, when the high affinity compounds have been solved in both A and B homodimer subunits and they absolutely match the corresponding units in the initially published apo X-ray structure (pdb id 1prg).
What is your opinion?
I read more about this topic and it seems that there isn't second "common" adopted hypothesis but, as I supposed, just poor reviews like this: Journal of Computational Medicine Volume 2013 (2013) http://dx.doi.org/10.1155/2013/406049 and unfortunately some misunderstanding in more serious papers like in Nat Struct Mol Biol. 2008 Sep;15(9):924-31...and several others which I cited above....
Probably it is more interesting whether dimerisation affects the second homodimer unit reshaping the H12 conformational landscape...
An another example, any comments? :) :
"Co-crystallization of 3 with hPPARγ LBD afforded a homodimeric complex, and X-ray crystallographic analysis at 2.1 Å resolution showed that one of the LBDs adopts a fully active structure identical with that in the complex of rosiglitazone, a full agonist; however, the other LBD in the complex of 3 exhibits a different (non-fully active) structure."....These results suggest hPPARγ partial agonists lack the ability to induce fully active LBD. The presence of at least one non-fully active LBD in the agonist complex may be a useful criterion to distinguish hPPARγ partial agonists from full agonists... Nevertheless, our results at least suggest that the presence of a non-fully active LBD in the agonist complex may be a useful criterion to distinguish hPPARγ partial agonists from full agonists."
http://www.sciencedirect.com/science/article/pii/S0960894X15004084#