December 18, 2010
3 New GPCR Structures Expected for 2011 (Maybe)
This year we’ve seen 2 new X-ray GPCR structures published, and the PDB now shows 27 entries (list here).
Let’s put this progress into a historical perspective: The first protein structure was published in 1960 (Kendrew et al.), the first membrane protein structure in 1985 (Deisenhofer, et.al) and the first GPCR structure appeared in the PDB in 2000 (Palczewski et al.). As of today the Protein Data Bank lists a staggering 69,967 entries (soluble and membrane protein structures, with a variety to techniques used), of these about 719 are membrane protein structures, of which 262 are unique.
What does that tell us for GPCR structures in 2011? One could reasonably expect to see two or three new unique GPCR structures in 2011 and maybe an additional 10 GPCR structures that are related to already determined ‘base structures’ (for instance the advertised antagonist bound b2AR structure). This estimate is a continuation of a trend that was first described by Richard Dickerson in 1978 for soluble proteins and then applied to membrane proteins by Stephen White (see here for Stephen’s fantastic Membrane Proteins of known 3D Structure site).
Figure: Progress of structure determination as tracked by the PDB and Stephen White’s site.
The numbers to extend this Dickerson-White law to GPCRs by fitting m = exp(by) are still somewhat shaky for GPCRs, but if the exponential trend holds true we could reasonably expect more than 2 and less than 3 unique GPCR structures in 2011 (one of them: S1P receptor). Another way to look at GPCR structural biology is that, compared to soluble proteins, GPCR structure determination is back in the mid nineteen seventies.
We’ve got a long way to go,
Peter
References
First Protein Structure:
KENDREW JC, DICKERSON RE, STRANDBERG BE, HART RG, DAVIES DR, PHILLIPS DC, & SHORE VC (1960). Structure of myoglobin: A three-dimensional Fourier synthesis at 2 A. resolution. Nature, 185 (4711), 422-7 PMID: 18990802
First Membrane Protein Structure:
Deisenhofer J., Epp O., Miki K., Huber R., and Michel H. 1985. Structure of the protein subunits in the photosynthetic reaction centre of Rhodospeudomonas viridis at 3 Å resolution. Nature 318:618-624.
First X-ray crystallographic structure of a G-protein coupled receptor:
Palczewski, K. (2000). Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor Science, 289 (5480), 739-745 DOI: 10.1126/science.289.5480.739