Note to Photo Editors: A slide show of recently determined protein structures is available with the Web version of this news release at http://www.nigms.nih.gov/news/releases/021005.html. For additional images, visit the new PSI Image Gallery at http://www.nigms.nih.gov/psi/imagegallery.html.
The Shapes of Life: NIGMS Project Yields More Than 1,000 Protein Structures
The Protein Structure Initiative (PSI), a national program aimed
at determining the three-dimensional shapes of a wide range of
proteins, has now determined more than 1,000 different structures.
These structures will shed light on how proteins function in many
life processes and could lead to targets for the development of
new medicines.
The PSI is a 10-year, approximately $600 million project funded
largely by the National Institute of General Medical Sciences (NIGMS),
part of the National Institutes of Health. The first half of this
project — a pilot phase that started in 2000 — has
centered on developing new tools and processes that enable researchers
to
quickly, cheaply, and reliably determine the shapes of many proteins
found in nature.
“One thousand protein structures is a significant milestone for
the PSI, and it shows an impressive return on the investment in
the technology and methods for rapid structure determination,” said
Jeremy M. Berg, Ph.D., director of NIGMS. “These structures
are interesting in their own right and provide the basis for modeling
many important proteins.”
Some of the newly determined structures are of proteins found
in plants, mice, yeast, and bacteria, including the pathogenic
types that cause pneumonia, anthrax, and tuberculosis.
The nine PSI pilot centers have transformed protein structure determination
from a mostly manual process to a highly automated one. Robotic
instruments rapidly clone, express, purify, crystallize, and
analyze many proteins simultaneously, cutting the time it takes
to determine a single protein structure from months to days.
For example, a robotic arm drops protein solution into thousands
of tiny wells for crystallization trials, and an imaging system
quickly scans the wells looking for signs of crystal formation — key
to capturing protein structures.
“At this large scale, it would be unthinkable to do all
these steps by hand,” said John Norvell, Ph.D., director
of the PSI at NIGMS and a scientist trained in protein structure
determination. He noted that some robotics and automated tools
have been refined and are now marketed by companies for general
structural biology applications.
As the PSI pilot centers have put automated structure determination
pipelines in place, the number of protein structures they have
solved has increased significantly. In the second, third, and fourth
years of the pilot phase, the centers in aggregate reported 109,
217, and 348 structures, respectively. Now, halfway through the
fifth year, they’ve surpassed a total of 1,000. Many of these
structures are very different from previously known structures,
said Norvell.
The findings contribute to the initiative’s ultimate goal
of providing structural information on 4,000-6,000 unique proteins
that represent the variety found in organisms ranging from bacteria
to humans. Researchers can use these structures, which are determined
experimentally, to build computer models of the structures of other
proteins with related amino acid sequences.
Although the main focus of the second phase of the PSI will be
on solving protein structures, Norvell said there will be continued
development of new technology: “As we reach for higher-hanging
fruit — protein structures that are more complex and harder
to solve — we will need to develop additional tools and methods.”
As part of the PSI effort, all the structures determined by the
centers are collected, stored, and made publicly available by the
Protein Data Bank (PDB), http://www.rcsb.org/pdb/, a repository
of three-dimensional biological structure data.
“The protein structures solved by the PSI are more than
a scientific stamp collection,” explained Norvell. “They
will help researchers better understand the function of proteins,
predict the shape of unknown proteins, quickly identify targets
for drug development, and compare protein structures from normal
and diseased tissues.” In general, a broad range of biomedical
researchers will benefit from the PSI’s technical advances,
experimental data, and availability of new materials, such as reagents.
“There are a lot of proteins that are incredibly important
to understanding human biology and medicine, yet we know very little
about most of them,” said Norvell. “The PSI will provide
important information about these molecules so vital to life.”
The nine pilot centers participating in the first phase of the
PSI are:
The pilot phase of the PSI will end in mid-2005. Centers for the
second phase will be announced in July 2005.
In addition to NIGMS, the PSI currently receives funding from the
National Institute of Allergy and Infectious Diseases, a component
of the National Institutes of Health.
For more information about the PSI, please visit http://www.nigms.nih.gov/psi/.
To schedule an interview with Jeremy M. Berg, Ph.D., or John Norvell,
Ph.D., please contact the NIGMS Office of Communications and Public
Liaison at 301-496-7301.
NIGMS is one of the 27 components of NIH, the premier federal agency
for biomedical research. The NIGMS mission is to support basic
biomedical research that lays the foundation for advances in disease
diagnosis, treatment and prevention.
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