New paper in PloS One:
Fatakia SN, Costanzi S, Chow CC (2011) Molecular Evolution of the Transmembrane Domains of G Protein-Coupled Receptors. PLoS ONE 6(11): e27813. doi:10.1371/journal.pone.0027813
G protein-coupled receptors (GPCRs) are a superfamily of integral membrane proteins vital for signaling and are important targets for pharmaceutical intervention in humans. Previously, we identified a group of ten amino acid positions (called key positions), within the seven transmembrane domain (7TM) interhelical region, which had high mutual information with each other and many other positions in the 7TM. Here, we estimated the evolutionary selection pressure at those key positions. We found that the key positions of receptors for small molecule natural ligands were under strong negative selection. Receptors naturally activated by lipids had weaker negative selection in general when compared to small molecule-activated receptors. Selection pressure varied widely in peptide-activated receptors. We used this observation to predict that a subgroup of orphan GPCRs not under strong selection may not possess a natural small-molecule ligand. In the subgroup of MRGX1-type GPCRs, we identified a key position, along with two non-key positions, under statistically significant positive selection.
6 thoughts on “New paper on GPCRs”
How’d you get into this particular topic? More through the biology, or more through the math? (Wasn’t sure whether I’d seen you write on this particular topic before.)
It’s a long story but it came about through collaborating with a computational chemist in the lab and have a fellow who was interested in it. Here are other posts on this.
A couple things from your earlier post:
“Most drugs in use today target GPCRs.”
Is there a breakdown somewhere that shows that?
“There are thousands of different types in humans alone.”
Are each of these coded by a different gene? Just wondering cuz “thousands” is roughly the same order of magnitude as the number of genes…
…OK, Wikipedia entry for GCPR claims that 40% of drugs target them.
…and same entry claims ~800 genes.
(Not that those #s are far off from yours)
I think there are more than 800 olfactory GPCR receptors so the Wikipedia entry must be ignoring those.
Actually, I think may have exaggerated the number of GPCRs. Anyway, it’s lots and they’re important.