Journal ReportJournal Report

2007.12.252007.12.25党新星、郭春芬、高迪党新星、郭春芬、高迪

ScientistsScientists

Raymond C. Stevens Brian K. Kobilka

About GPCRsAbout GPCRs• GPCRs communicate signals across cell

membranes in response to an astonishing variety of extracellular stimuli—light, proteins, peptides, small molecules, hormones, and ions. Once activated, GPCRs trigger a cascade of responses inside the cell, primarily through interactions with their G protein partners.

About GPCRsAbout GPCRs As we know, GPCRs share a common structura

l signature of seven membrane-spanning helices with an extracellular N terminus and an intracellular C terminus . They are remarkably versatile signalling molecules that are responsible for the majority of transmembrane signal transduction in response to hormones and neurotransmitters.

Why we work for GPCRWhy we work for GPCR Nowadays, what we care most is nothing

but health. And GPCRs just have specific functions for drugs .

Specific function for drugsSpecific function for drugs• Drugs that act on GPCRs cover more tha

n a half of current market for human therapeutics, with annual income over $40 billion.

Specific function for drugsSpecific function for drugs Current asthma( 哮喘病 ) drugs that invol

ved in adrenergic receptors often have undesirable side effects. Structures of GPCRs can guide the development of more specific drugs and can be combined with traditional chemical screening methods to improve and accelerate drug discovery.

Challenges in crystallizing GPCRsChallenges in crystallizing GPCRsIt is hard to express in vitro.Even expressed, it is not abundant.GPCRs are not stable and easy to be inacti

ve. The purification is hard.The structure is too loose to crystallizing.

How to solveHow to solve• b2AR(a kind of human GPCRs) was expre

ssed in Sf9 insect cells, solubilized( 溶解 ) in 1% dodecylmaltoside, and purified by sequential antibody and ligand affinity chromatography （配体亲和色谱仪） . Following the reported success with microbial rhodopsins （视紫红质） in lipidic cubic phase (LCP)

• My part is over.• Thank you!