A collaboration between investigators at Purdue University and Catholic University of America has uncovered the mechanism behind a critical movement that some pathogenic viruses, including herpes, exhibit.
Parts of the motor move in sequence like the pistons in a car’s engine, progressively drawing the genetic material into the virus’s head, or capsid, said Michael Rossmann, Purdue’s Hanley Distinguished Professor of Biological Sciences.
The motor is needed to insert DNA into the capsid of the T4 virus, which is called a bacteriophage because it infects bacteria. The same kind of motor, however, also is likely present in other viruses, including the human herpes virus.
"Molecular motors in double-stranded DNA viruses have never been shown in such detail before," said Siyang Sun, a postdoctoral research associate working in Rossmann’s lab.
Other researchers have determined that the T4 molecular motor is the strongest yet discovered in viruses and proportionately twice as powerful as an automotive engine. The motors generate 20 times the force produced by the protein myosin, one of the two proteins responsible for the contraction and strength of muscles.
The virus consists of a head and tail portion. The DNA-packaging motor is located in the same place where the tail eventually connects to the head. Most of the motor falls off after the packaging step is completed, allowing the tail to attach to the capsid. The DNA is a complete record of a virus’s properties, and the capsid protects this record from damage and ensures that the virus can reproduce by infecting a host organism.
Sun determined that the packaging motor is made of two ringlike structures, and both of these discs contain five segments made of a protein called gp17, for gene product 17. The researchers determined the atomic structure of these protein segments using a procedure called X-ray crystallography. They also used another technique called cryo-electron microscopy, which enabled them to see a more distant, overall design of the motor’s ringlike structure.
One disc sits on top of the other, and each of the five segments of the top disc shares a gp17 protein with a corresponding segment in the bottom disc. The gp17 proteins have two segments, or domains, one segment in the lower disc and the other segment in the upper disc.
The lower disc first attaches to the DNA and is then drawn upward by the upper disc, pushing the DNA into the virus’s capsid in the process. The top disc of the motor pulls the lower disc upward using electrostatic forces generated between oppositely charged objects, Rossmann said.
"These findings determined the relationship between the motor and DNA," Rossmann said.
The research data also showed that the motor is dynamic and apparently exists in two states: relaxed and tensed, the latter likely occurring when the top disk has attracted the lower disc.
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Image: The image shows a cross section of the virus head, or capsid, and an artist’s interpretation of the motor as it packages DNA into the virus. The hands represent the five segments of the ringlike structures. Each hand takes a turn grabbing the DNA and moving it into the head until the head is full. [The journal Cell, Dec. 26, 2008; Steven McQuinn, independent science artist, and Venigalla Rao, The Catholic University of America.]