I am pleased to see you D3R.
Science. 2010 Nov 19;330(6007):1091-5.
Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist.
Chien EY, Liu W, Zhao Q, Katritch V, Han GW, Hanson MA, Shi L, Newman AH, Javitch JA, Cherezov V, Stevens RC.
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
.. and my hat-off to you all above there.
Here are some pictures of the D3 dopamine receptor-lysozyme chimera in rainbow colours: dark blue (TM1), blue (TM2), turquoise (TM3), green-blue (TM4), green (TM5), yellow-orange (TM6), orange-red (TM7), red (helix 8). PDB file was visualised using UCSF Chimera v. 1.4.1 (University of California, San Francisco).
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Fig.1. Looking TM1, helix8 |
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| Fig. 2. Viewed from TM2 side |
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| Fig. 3. Looking TM3, 4 and 5 |
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| Fig. 4. Facing TM4 |
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| Fig. 5. Looking TM5 and 6 |
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| Fig. 6 . Looking TM6, 7 and helix8 |
Yes we know that it looks all pretty, but my favourites in particular are Fig. 3. and Fig. 6: both showing the long, relatively straight TM3 laid beautifully as if a pivot of the helical bundle.
This crystalised D3R was stabilised by the antagonist and also with a residue substitution at TM3 at position 119: the original Leu was substituted with Trp (rhodopsin naturally has Trp there). Stevens group has previously demonstrated in beta 2-adrenergic receptor that the residue substitution at the corresponding position favours thermodynamically to maintain the bundle integrity / protein architecture. Hey there it worked again!
Some misery guts may say: “oh we’ve already got enough templates for homology modelling; is it worth crystalising anymore class/Family A GPCRs?” - whatever their arguments are, I don’t think that these are relentless efforts that bring little new, yet at this time, especially for this one which has been a good empirical proof regarding their previous findings.
