In a multicellular
organism, such as a human, cells must communicate with one another to
coordinate their activities across the entire organism. Cells send messages
to each other through signaling compounds that attach themselves in
lock-and-key fashion to protein receptors present both on cell surfaces
and inside cells. These signaling compounds include proteins, hormones,
peptides, amino acids, and even dissolved gases.
An example of
a signaling compound is the hormone estrogen, which swims around in
circulating blood and interacts with its receptors located on the surfaces
of cells within the endocrine system. Some small signaling compounds
can pass through the cell membrane to interact with a receptor inside
the cell, while others remain tightly bound to the surface of one cell
and interact with receptors bound to the surface of a neighboring cell.
Characterizing the details of these and other types of interactions
of biomolecular complexes is the chief goal of a new DOE user facility
at ORNL, the Center for Structural and Molecular Biology (CSMB). Michelle
Buchanan, associate director of ORNL's Life Sciences Division (LSD),
also serves as director of the CSMB. The CSMB includes scientists from
LSD and from ORNL's Chemical and Analytical Sciences (CASD) and Solid
State divisions, as well as from Los Alamos National Laboratory (LANL).
conception of the cold neutron source–hydrogen moderator vessel,
which is being built in 2000 and will be installed in 2001 in
ORNL's High Flux Isotope Reactor. Neutrons from the reactor are
slowed down by frequent collisions with the moderator’s hydrogen
atoms. Because the collisions heat up the hydrogen, it must be
cooled down by a helium refrigerator to remain an effective neutron
moderator. The moderator vessel cutaway (above) shows the temperature
of representative hydrogen flow streams.
"The new center
is based on our traditional strengths in neutron science, mass spectrometry,
and computational sciences," Buchanan says. "Our mass spectrometry and
computational sciences capabilities are now open to outside researchers."
DOE's Office of
Biological and Environmental Research supports the CSBM and is providing
nearly $6 million to build a biological small-angle neutron scattering
(Bio-SANS) instrument, which should be functioning by June 2002. Bio-SANS
will be added to the guide hall of the new cold neutron source now being
constructed at ORNL's High Flux Isotope Reactor (HFIR).
SANS instrument will be designed to have both high flux and low background,
which is critical to the analysis of biological materials," Buchanan
says. "The upgrade of the HFIR offers a unique opportunity to provide
the biological community with a SANS facility that rivals the best capabilities
in the world.
"X-rays give excellent
high-resolution analysis of the structure of proteins in crystals,"
she says. "But some very important proteins cannot be crystallized.
Also, scientists use nuclear magnetic resonance (NMR) and SANS to study
these proteins in their natural form, in solution. Results from the
Bio-SANS will not only complement data obtained from X-ray crystallography
and NMR but also will provide unique information on the interactions
of biomolecules in complexes involved in the cell-signaling processes."
and Biological Mass Spectrometry Group has added several new mass spectrometers
to supplement its current capabilities, including a high-performance
Fourier transform ion cyclotron resonance (FTICR) instrument.
"The new FTICR
is equipped with an electrospray ionization source, which will allow
us to study large proteins and protein complexes," says Buchanan. "The
instrument was delivered with a 7-Tesla superconducting magnet. It will
be upgraded this summer with a 9.4-Tesla magnet, which will increase
the performance of the instrument with respect to both mass resolution
and dynamic range. We are very excited about having this instrument
for biological studies."
Protein Structure Group, which predicts protein folding and threading
using sophisticated computer models, will assist with interpreting data
on biomolecules obtained by researchers using SANS. This group will
work closely with researchers at LANL to provide users with user-friendly
software for the interpretation of data.
a bright future ahead for the new CSMB. "We are just beginning to get
the word out about the CSMB and have already had researchers from the
University of Tennessee come to use the mass spectrometry resource."
between scientific facilities and users may be just as important as
it is between cells in multicellular organisms.