#leftkowitz

[pharmtastic]

Further data on GPCR-arrestin interaction

Another interesting (and well written) study that 'needs' to be shared is the nature paper ("Visualization of arrestin recruitment by a G-protein-coupled receptor") on the interactions between g-protein coupled receptors and arrestin from Lefkowitz and collaborators. This time they turned to hydrogen deuterium exchange and electron microscopy combined with some complex 3D reconstructions to understand the protein dynamics of receptor-arrestin interactions.

A couple of things (with valid reasons) that I found really interesting was the use of Vasopressin receptor with some structural modifications including a N-terminal T4Lysozyme as the token GPCR for this study. The other being the use of a nanobody to stabilize the ligand-receptor-arrestin complex. This study not only confirmed some of the previous EPR studies but also reveals other changes in the N- and C-terminus of beta-arrestin. They move on to suggest a biphasic mechanism of arrestin recruitment, which sounds very plausible considering it is very similar to the g-protein mechanism. 

On a secondary note, the number of failed techniques/constructs to study this collossus protein complex, pile on as you continue reading down the paper, which makes this study all the more impressive. Looking forward to more (crystal structure of the complex?) from these guys in the near future.

[pharmtastic]

Noble prizes?

I'm spending the night at the lab to finish up some writing work but having done with it earlier than expected I thought why not add a new post. Yes, its been a while but hey I still remember the password to my tumblr account! 

I never got around to writing about the Nobel prize in chemistry this year which was awarded to the grandfather of GPCRs, Bob Leftkowitz sharing it with his protege Brian Kobilka. I will not dwell too much into whether they deserved it or what exactly won them the award, as a number of fellow bloggers and science journalists have dealt into this in great detail over the past few months. But I would like to make just one point that if you can spare about 50 mins, I would recommend watching their Nobel interview -  

http://www.nobelprize.org/mediaplayer/index.php?id=1860

The stark contrast in their demeanor during the interview is very interesting and is rather intriguing as to how they managed to get along over the years with such a massive difference in personalities (as pointed our by Bob himself). It is my belief that 'it' (it being this combined, massive undertaking of GPCRs that took over 40 years) would never have been such as success if Kobilka was the predecessor with Bob being his student. This is no offense to Kobilka's mentorship skills.

Anyway, lets move on to another monetary prize that has raised some eyebrows in the recent weeks - The Life science breakthrough prize!! The $3 million award to a select few scientists focusing on 'breakthrough' therapeutic strategies mainly targeting cancers and some neuro-degenerative diseases has elicited a rather bitter and unwarranted antipathy. I couldn't disagree more with this aversion towards awarding such large sums of money to a select few.

First and foremost, it is a privately funded award trying to encourage rapid development of therapeutic strategies for some diseases that could potentially wipe out the human race in the coming years unless they are conquered soon. Secondly, the wide (and rightly so) distribution of federal money although has given numerous breakthroughs over the years, have come along in far too few numbers and too far apart. This monetary push from these tech magnates with stuffed wallets may turn out be the push that has been missing in this field.