One of nature's smallest motors helps viruses package their genetic material, according to research described in the December 7 issue of the scientific journal Nature.
Scientists at Purdue University and the University of Minnesota have solved the three-dimensional structure of the central component of a biological motor that powers the DNA packaging system in a virus, providing scientists with their first glimpse of such a motor system. The study revealed how the core of a tiny motor, just millionths of a millimeter in size, is constructed and suggests how it works to pack long stretches of the virus' genetic material into its outer shell during the process of viral replication.
The work was made possible in part by the National Science Foundation (NSF), through its Molecular Biophysics program. The results point to new opportunities in nanoscience, according to NSF program director Parag Chitnis. "One application of this work will be in developing drugs that would inhibit virus replication. Many viruses that infect humans, such as Herpes, use a similar machinery for DNA packaging," he said.
The project may provide clues as to how DNA is packaged in similar viruses - including Herpes virus, which causes human ailments such as Herpes simplex, chicken pox and shingles - and suggest ways for developing drugs that prevent illnesses caused by viral pathogens.
"This study provides the first knowledge of a DNA packaging motor," said Michael Rossmann, Hanley Distinguished Professor of Biological Sciences at Purdue. "Though other motor systems have been studied in biology, this is the first motor known to translocate genetic material."
Viruses are essentially a simple parasite consisting only of an envelope that contains the genetic material ready for transportation from one host to another. They can reproduce only after infecting a host cell. Once inside a cell, the virus manipulates the cell's machinery to produce all the necessary components, including genetic material, to assemble new viruses. It is here that the biological motor is needed to fill newly assembled envelopes with their genetic material, Rossmann said. The new viruses are then released from the host cell and are free to infect other cells.
The study also will provide scientists with new insights on how molecular motors work in biology, said Dwight Anderson, professor at the University of Minnesota.
"The beauty of phi29 motor is that it provides a relatively simple system to investigate the mechanism of DNA packaging," Anderson said. "Working in a micro-droplet, or an area the size of a very small drop, the motor packages a DNA about 130 times longer than the viral shell, in just three minutes.
In the study, Rossmann, along with Purdue researcher Timothy Baker and others at Purdue, and Anderson and his co-workers at Minnesota, used micro-imaging techniques - including X-ray crystallography and cryo-electron microscopy - to determine the structure of the DNA packaging motor in a virus called Bacteriophage phi29.
Bacteriophages are viruses that only infect bacteria. They are widely used in laboratory research because they are often similar in structure to human viruses.
The research was also funded by the National Institutes of Health and Purdue University.
Media contacts:
Tom Garritano
703-292-8070
tgarrita@nsf.gov
Purdue:
Susan Gaidos
765-494-2081
sgaidos@purdue.edu
Program contacts:
Parag Chitnis
703-292-8443
pchitnis@nsf.gov
Michael Rossmann
765-494-4911
mgr@indiana.bio.purdue.edu