Ladies and Gentleman, the winners have been announced!
Robert J. Lefkowitz (left) and Brian K. Kobilka (right) |
At 2:30AM this morning in California, the recipients of the
Nobel Prize in Chemistry were called and informed of their accomplishments.
Robert J. Lefkowitz, 69, and Brian K. Kobilka, 57, have discovered the
molecular workings and structures of G protein-coupled receptors (GPCRs). GPCRs
are a family of proteins that have been discovered to be the transmitters of
critical biological messages for functions such as vision, smell, taste, and
neurotransmission.
The two men set out on their scientific journey in an
attempt to understand the biological processes that occur during a body’s
production of stress hormones, such as adrenaline. Science already uncovered what
happens to a person when the hormones are produced; a receptor is bound by the
hormone and then a person experiences focused vision, quickened breathing,
diverting blood from the less important body systems etc. The groundbreaking
aspect of Lefkowitz and Kobilka’s findings is that the nature of the receptors
for these hormones are now known.
Lefkowitz first traced the signaling of these receptors in
the 1970s with radioactive blocking agents attached to hormones. By marking the
hormones, Lefkowitz was able to follow where they attached in the body and
observe the activities of the receptors they attached to. With much effort, Dr.
Lefkowitz was able to identify the receptor proteins and prove they were
specific molecules.
In the 1980s, Lefkowitz’s group at
Duke University, which Kobilka was a part of, found the gene that actually
produced one of the protein receptors. The group saw that the shape of the
protein had many long spirals that wove through the cell membrane exactly seven
times.
3D image of rhodopsin. |
Realizing that
the receptor he discovered had the same characteristic seven helicies as
another receptor that had been found in the retina, in this case the light
receptor rhodopsin, Lefkowitz and his team set out to find several other
similar receptors that were found to be in a family of receptors, called the G
protein-coupled receptors. Today, about a thousand of these GPCRs are known.
They reside on the surface of cells and react to a host of hormones and
neurotransmitters. Dr. Kobilka moved to Stanford and progressed to
determine the three-dimensional structure of the GPCRs, which involved the
utilization of x-ray crystallography.
“We hope
by knowing the three-dimensional structure we might be able to develop more
selective drugs and more effective drugs,” Dr. Kobilka said. The ultimate goal with all this new
information is to refine drug design. Many drug molecules attach to cells, not
only at the intended target, but also to other receptors. This may help eliminate those unwanted side
effects that one experiences when taking certain drugs.