Cold
Neutrons for Biology and Technology
Stephen H.
White: UC-Irvine (UCI) professor of biophysics and leader of
the CNBT project, White is working to explain the fundamental principles
that govern the folding and stability of cell membrane proteins.
The ultimate aim of White’s laboratory is to predict the detailed
three-dimensional structure of membrane proteins from their constituent
sequence of amino acids, the building blocks of proteins. White
will use “cold neutron” probes and molecular dynamics
simulations to reveal the complex interactions that occur as proteins
and protein fragments, first, bind themselves to the sandwich-like
cell membrane and, then, assume their final shape. At first, White
will focus on two proteins: melittin, a component of bee venom that
winds like a corkscrew through the bilayer membrane, and indolicidin,
a linear peptide with antibiotic properties.
Huey W. Huang:
Professor of physics and astronomy at Rice University, Huang has
developed methods for investigating in-plane structures in membranes.
Using neutron scattering, he has detected transmembrane pores induced
by disease-fighting membrane-active peptides. These antimicrobial
peptides can exist in either of two states. In the active state,
they form pores in the membrane. In the inactive state, the peptides
are embedded in the lipid head groups on the membrane surface. With
the CNBT’s instruments, Huang will examine structural changes
that occur during the shift from one state to the other as well
as factors that trigger the transition. Among the peptides that
Huang will study are those related to human defensins—part
of the body’s first line of defense against microbe invaders—and
those with potential for pharmaceutical applications.
Douglas Tobias:
UCI assistant professor of chemistry, Tobias is developing approaches
to simulate membrane-protein interactions at the level of individual
atoms. His laboratory’s simulations account for such influencing
factors as temperature, membrane pressure, and electrostatic forces.
Tobias will use data from CNBT experiments as a reality check and
to refine and extend the models that underlie his molecular dynamics
simulations. Initially, Tobias will focus on melittin, indolicidin,
and Vpu, a disruptive protein produced by one type of the AIDS-causing
human immunodeficiency virus (HIV-1). Simulation techniques refined
or developed during these experiments should be applicable to a
wide variety of membranes and proteins.
J. Kent Blasie:
University of Pennsylvania professor of physical and biological
chemistry, Blasie and his Penn collaborators have developed methods
for making simple analogs of complicated membrane proteins. These
so-called maquettes are easy to modify—a boon to efforts to
determine their structure and mechanism of action compared to their
more intricate counterparts. They also are being eyed for use as
biomolecular devices. In the CNBT project, Blasie will investigate
membrane protein maquettes that perform vectorial electron transfer
reactions, and he will study how Vpu, an HIV-1 accessory protein,
contributes to the proliferation of the virus in the bodies of infected
people.
Susan Krueger
and Charles Majkrzak: Krueger, a NIST biophysicist, and Majkrzak,
a NIST physicist specializing in instrument design, have pioneered
new neutron-based methods for surveying the cell membrane landscape
and for measuring its features. This makes it possible to probe
membrane-like samples in a fluid environment, akin to conditions
in the body. Other payoffs include increased resolution and easier-to-interpret
experimental data. They and NIST colleagues recently reported a
new, high-resolution technique that may greatly simplify efforts
to measure the depth and orientation of peptide fragments within
membranes. Krueger and Majkrzak aim to optimize the new technique,
using melittin and alpha-hemolysin, a barrel-shaped protein secreted
by some strains of staphylococcus bacteria.
Thomas J.
McIntosh: Professor of cell biology at the Duke University Medical
Center, McIntosh studies how the composition of the two lipid layers
that make up cell membranes affects the shape, organization, and
binding of proteins. A key area of interest in the CNBT project
will be the top-most layer of mammalian skin, which, among other
things, influences the effectiveness of drugs and other treatments
applied to the skin.
John F. Nagle:
Professor of biophysics at Carnegie Mellon University, Nagle aims
to explain the organization of lipid molecules in cell membranes.
On average, lipids make up about half the mass of a cell membrane,
but actual amounts of these fatty acids vary greatly among membrane
types. What accounts for this diversity in lipid composition is
unknown. To answer this question, Nagle has gathered data using
an array of experimental techniques. Without sustained neutron diffraction
studies, however, key pieces of information have been out of reach.
Ultimately, Nagle intends to construct time-averaged pictures showing
how lipids are organized in a cell membrane and to measure nanometer-scale
changes in membrane structure.
Anne Plant:
A NIST biotechnology researcher, Plant and colleagues have devised
methods for making rugged imitations of complex cell membranes.
Stable in air and liquid, these membrane mimics can support a variety
of research-and-development pursuits: studies of the structure and
function of cell-membrane proteins, development of miniature biosensors
and diagnostic devices, pharmaceutical screening, and tissue engineering.
In addition to furthering her own research on cell-membrane receptors,
Plant, along with other scientists in NIST's Biotechnology Division,
will supply CNBT collaborators with fabrication and analytical tools.
Other CNBT
Collaborators:
Stanley
Opella, Resource for Solid-State NMR of Protein, University of
California-San Diego
Klaus Gawrisch,
National Institute of Alcohol Abuse and Alcoholism, National Institutes
of Health
Michael Klein,
Materials Science and Engineering Center, University of Pennsylvania
National Stable
Isotope Resource, Los Alamos National Laboratory
Go
to News Release
Date created:
2/19/2002
Last updated:
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Contact: inquiries@nist.gov
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