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Journal Report
2007.12.25
党新星、郭春芬、高迪
Scientists
Raymond C. Stevens
Brian K. Kobilka
About 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 GPCRs
As we know, GPCRs share a common
structural signature of seven membranespanning 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 GPCR
Nowadays, what we care most is
nothing but health. And GPCRs just
have specific functions for drugs .
Specific function for drugs
• Drugs that act on GPCRs cover more
than a half of current market for
human therapeutics, with annual
income over $40 billion.
Specific function for drugs
Current asthma(哮喘病) drugs that
involved 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
GPCRs
It is hard to express in vitro.
Even expressed, it is not abundant.
GPCRs are not stable and easy to be
inactive.
The purification is hard.
The structure is too loose to
crystallizing.
How to solve
• b2AR(a kind of human GPCRs) was
expressed 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)
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My part is over.
Thank you!