Dec. 24, 2008

CUA and Purdue Scientists Discover Structure of Viral Nanomotor

Findings Detailed in Article Slated for Dec. 26 Issue of Journal Cell

From left, Zhihong Zhang, graduate research assistant; Venigalla B. Rao, professor of biology; Kiran Kondabagil, Istiaq Alam and Bonnie Draper, all postdoctoral researchers; and Shylaja Hegde, graduate student, in a lab at CUA’s McCort-Ward Hall.

WASHINGTON, D.C. — Researchers at Catholic University and Purdue University have discovered the atomic structure of a powerful nanomotor that packages DNA into the “head” of some viruses during their assembly, an essential step in their ability to multiply and infect new host organisms.

In addition, Kiran Kondabagil, Bonnie Draper and Istiaq Alam, all CUA postdoctoral researchers, and CUA Professor of Biology Venigalla B. Rao, along with Purdue researchers, have proposed a mechanism for how the motor works in a paper to be published in the Dec. 26 issue of the journal Cell.

Moving in sequence like the pistons in a car’s engine, parts of the motor progressively draw the genetic material into the virus’s head, or capsid, said co-author Michael Rossmann, Purdue’s Hanley Distinguished Professor of Biological Sciences.

Because of the motor’s powerful strength — to scale, twice that of an automobile — the new findings could one day inspire engineers designing sophisticated nanomachines. In addition, because the motor may be present in a number of virus types, including herpes, the research may also assist pharmaceutical companies as they try to develop methods to sabotage virus machinery.

The lead authors of the paper to be published in Cell, one of the highest rated journals in biology, are Kondabagil, a research assistant professor who works in Rao’s lab, and Siyang Sun, a postdoctoral research associate working in Rossmann’s lab at Purdue.

“This research is allowing us to examine the inner workings of a virus packaging motor at the atomic level,” Rao said. “This particular motor is very fast and powerful.”

The team of scientists used the T4 virus, which infects the E. coli bacteria, and, therefore, is known as bacteriophage. T4 has been a historically important model to understand how viruses are assembled. The Catholic University researchers isolated the virus components and performed biochemical analyses while the Purdue researchers studied the structures.

Not all viruses have motors such as those found in the T4, but some viruses that cause human diseases, such as herpes, possess molecular motors that have the same function and are likely to have similar structures.

The researchers found that the motor is located at the intersection of the capsid and the virus “tail” and is made of a circular array of proteins called gene product 17 (gp17). Five, two-part, gp17 proteins combine to form a pair of conjoined rings, arrayed so that their upper segments form an upper ring and their lower segments form a lower ring.

As a virus assembles itself in a suitable environment, the lower ring of the motor structure attaches to a strand of DNA, while the upper ring attaches to a virus capsid.  The upper and lower rings have opposite charges, which allow the motor to contract and release, alternately tugging at the DNA like a ring of hands pulling on a rope. 

The process draws the DNA strand upward into the capsid, where it is protected from damage, enabling the virus to survive and reproduce. After the DNA is inside the capsid, the motor falls off, and a virus tail attaches.

Until now, researchers did not know how the DNA packaging was accomplished by the T4 or any other virus.

Along with Sun, Kondabagil, Draper and Alam, the authors of the paper include Purdue electron microscopist Valorie D. Bowman; Zhihong Zhang, a CUA graduate research assistant; CUA graduate student Shylaja Hegde; Andrei Fokine, a Purdue postdoctoral research associate; Rossmann; and Rao.

The research has been funded primarily by the National Science Foundation and the Human Frontier Science Program.

Journalists can obtain a copy of the paper by calling Cathleen Genova at the journal Cell at 617-661-7057 or by e-mailing: cgenova@cell.com.

MEDIA: To arrange interviews with CUA researchers, reporters should contact the Office of Public Affairs at 202-319-5600.

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