Nobel 2012: GPCRs – Sensation(al) Receptors

GPCR proteins undergo changes in their shape (conformation) upon ligand binding. Rhodopsin in the eye retina detects light using its photon-sensitive retinal moiety, while olfactory receptors detect fragrant molecules, which we breathe in. In both cases this triggers signals, which are processed by our brains into senses of vision and smell (to examine more scientifically correct cartoons of GPCR signalling dangerous intellectuals should press the links I provided below)

The 2012 Nobel Prize in Chemistry was awarded to Robert J Lefkowitz and Brian K Kobilka for their mechanistic work on G-protein-coupled receptors or GPCRs.

This couldn’t possibly cause more yawning than it did. WTF? GPCRs? X-ray crystallography? What’s with all this jargon?  Scientific American and other pop-sci blogs gave the public some perspective of what the whole fuss is about.

GPCRs or G-protein coupled receptors – are a type of protein molecules stuck at the surface of our cells, which can sense almost anything – light, odour, pheromones, neurotransmitters, adrenalin, cannabis, etc.

Basically, we knew about GPCRs for decades. Almost a third of all pharmaceutical drugs (hundreds of thousands) target these receptors. Yet before these guys rolled up their sleeves and did some work, we knew nothing about the structure of these receptors, and how GPCR signalling is triggered to let the cell know about changes in environment.

So, the two Americans and many other labs have done hundreds of biochemical and biophysical experiments, deducing structures of these molecules.

But what’s in it, you may ask?  You see the problem is most of the current drugs have tons of side effects, they are not very specific, meaning they can interact with more than one GPCR  or possibly even other proteins.  If we know in detail the structure of a given receptor we can then design highly specific and less toxic drugs.

You may not know that but this 2012 Nobel is not the first one for work done on GPCRs.

In 1967 George Wald was awarded for his discovery of the “light” receptor, rhodopsin,   which belongs to GPCR family. He found that vitamin A is transformed in our body into a retinal molecule, which binds a protein called opsin  in the eye retina and forms a light sensitive rhodopsin. This explains why vitamin A deficiency caused blindness.

In 1994 Linda Brown Buck got her Nobel for discovery of olfactory receptors, which detect smells in your nose. These also turned out to belong to the GPCR family of cell surface receptors.

GPCRs are extremely abundant in all organisms, in humans there’re over 800 different types of them capable of responding to thousands of compounds.  The question, which I find interesting, is where this amazing variety originated from and how  did it evolve? It’s a nerdy question I know.

In bacteria there’s a bacteriorhodopsin, which is only structurally similar to our vision receptor, but no other GPCRs were found there.  So, how did we get hundreds of ours?

A recent study might have found a bacterial cousin of all animal GPCRs, it’s called FeoB and bacteria use it to uptake iron from the surroundings.

The world is full of surprises, and just think about how it astonished and frustrated the public when Darwin said 150 years ago that we descend from monkeys. So what? A billion years ago our ancestors were just some tiny bacteria.  But that’s for another blog, because now I need to hide from a bunch of angry creationists.  Only joking.

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  • Ashen

    G-protein-coupled receptors are GPCRs. OK, at least it’s not a secret language, only a condensed one :) All taken apart and named, there’s but one conclusion, humans are amazing,

    • GrigoryRyzhakov

      and some of them like Ashen are super-amazing :)