Source: Purdue University
Purdue Researchers Expose 'Docking Bay' For Viral Attack
WEST LAFAYETTE, Ind. - Imagine a virus and its cellular target as two
spacecraft - the virus sporting a tiny docking bay that allows it to invade
its victim. Purdue University researchers have taken a close-up picture of
one virus' docking bay, work that could have implications for both medicine
Using advanced imaging techniques, an international team of biologists led
by Michael Rossmann of Purdue, Vadim Mesyanzhinov in Moscow and Fumio
Arisaka at the Tokyo Institute of Technology has analyzed the structure of
part of the T4 virus, which commonly infects E. coli bacteria. The part they
analyzed, called the baseplate, is a complex structure made of 16 types of
proteins that allows T4 to attach itself to the surface of E. coli in order
to inject its own deadly genetic material. Their work has produced the
clearest picture ever obtained of the baseplate, which plays a critical role
in the initial stages of viral infection.
"We now have a fairly complete picture of the baseplate, the part of the
virus that latches onto its cellular victim," said Rossmann, who is Hanley
Distinguished Professor of Biological Sciences in Purdue's School of
Science. "Armed with this knowledge, we should obtain a better understanding
of how this virus injects its genetic material into its host. It could be
the key to stopping the process - or even harnessing it to benefit
The paper appears in the latest issue (Sunday, 8/17) of Nature Structural
While T4 is perhaps not as well known as the viruses that cause the flu, it
is an old friend of viral researchers as an invader of the E. coli
bacterium, which itself can threaten human health. Viruses that attack
bacteria, called bacteriophages, are readily studied because a virus that
attacks a unicellular host can often be observed and manipulated more
"Mesyanzhinov, Arisaka and I discussed the possibility of examining T4 in
closer detail," said Rossmann. "It's a very complicated structure consisting
of more than 150 protein molecules, and we wanted to know how they were put
together. So we decided to take a close look."
It had been common scientific knowledge that the baseplate was a complicated
but beautiful mechanism, one which changed its conformation from a hexagon
to a star shape as it formed the irrevocable bond between virus and
bacterium. Analysis of its protein building blocks required the use of both
electron microscopy, needed to resolve the shapes and relationships between
the proteins, and X-ray crystallography, needed for high-resolution images
of the atoms within them. Each of the three researchers contributed some of
the technology necessary for the analysis, which eventually revealed the
structure of the baseplate.
"There are several steps a virus takes to infect a host cell," Rossmann
said. "Scientists have long known what the steps were, but no one had ever
examined them on a molecular level before. This research should allow us to
analyze the initial events in a viral attack. Such knowledge could be useful
for targeting bacterial viruses to kill invading bacteria as an alternative
to antibiotic compounds."
While viruses are not generally thought of as prospective friends to
mankind, many attack the very bacteria that cause common human illnesses,
giving them potential as antibiotics.
"T4 attacks E. coli, which is well known as a threat to human health,"
Rossmann said. "Many other bacteriophages also have structures similar to
T4. If we could modify the proteins in the baseplate's attachment fibers, it
might enable T4 to destroy harmful bacteria. This research could be a step
in that direction."
Nanotechnology applications also are possible.
"The baseplate of this virus is essentially a complex molecular machine,"
Rossmann said. "We have now obtained a clear picture of its structure, which
has allowed us to suggest how it works. Building nanomachines will likely be
easier if we can borrow some mechanisms already proven by nature."
Such applications are admittedly pie in the sky for the moment, and Rossmann
said the most valuable result of the research is the fundamental knowledge
it reveals about viruses.
"We now have a close-up image of the machinery that guides the steps taken
when a virus infects a cell," he said. "We hope further analyses will show
even greater detail."
This research was funded in part by grants from the National Science
Foundation, the Howard Hughes Medical Institute and the Human Frontiers
Rossmann's team is associated with Purdue's Markey Center for Structural
Biology, which consists of laboratories that use a combination of
cryoelectron microscopy, crystallography and molecular biology to elucidate
the processes of viral entry, replication and pathogenesis.
Editor's Note: The original news release can be found here.
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