NSF PR 00-36 - May 24, 2000
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Membrane Protein Research Yields New Insights into
Inner Workings of the Cell
Biophysicists at the National Science Foundation’s
National High Magnetic Field Laboratory in Tallahassee,
Florida, have discovered that membrane proteins give
rise to unique patterns of signals in their nuclear
magnetic resonance (NMR) spectra. This result opens
a new approach for the three dimensional characterization
of membrane protein structures.
Membrane proteins are responsible for communication
between the external cellular environment and the
cell’s interior where chemistry and biological functions
are typically accomplished. Membrane proteins are
often responsible for cellular recognition and for
the transport of nutrients into and products out of
cells. However, these important proteins have been
particularly difficult to characterize by standard
technologies and hence few membrane protein structures
are known today.
"About 25 percent of proteins are membrane proteins,
yet structures of only few of these are known," says
Kamal Shukla, director of NSF's molecular biophysics
program, which funded the research. "X-ray crystallography
and solution NMR cannot be used for these proteins
because they are hard to crystallize and are not soluble.
The methodology developed by Cross and his colleagues
for obtaining structural information of integral membrane
proteins is therefore exceedingly important."
It has been known for some time that structural constraints
from solid state NMR spectroscopy of uniformly aligned
samples can be used to develop a high resolution three-dimensional
structure. However, while many constraints can be
obtained there has been no approach for dependable
resonance assignments. In other words, without knowing
where in the molecule each signal comes from it has
been difficult to make progress with structural characterization.
Now, researchers Tim Cross, Riqiang Fu and Jack Quine,
and their coworkers, supported by the NSF’s molecular
biophysics program, have discovered that the signal
patterns observed in two dimensional spectra directly
reflect the distribution of amino acids about a helical
axis, known as a helical wheel. Through standard methods
of isotopic labeling using bacterial cultures, it
is now possible to assign these signals to specific
atomic sites in the membrane protein helices.
Furthermore, the location of the resonance patterns
in the spectrum defines the tilt of the helix within
the membrane. Indeed, it is possible to get this topological
information on a helix without signal assignments
- the first time this has been possible in NMR spectroscopy.
These results have been published as the cover story
in the May 2000 issue of the Journal of Magnetic
Resonance.
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