Bacterial protein mimics host to cripple defenses

December 22, 2005

Like a wolf in sheep's clothing, a protein from a disease-causing bacterium slips into plant cells and imitates a key host protein in order to cripple the plant's defenses. This discovery, reported in this week's Science Express by researchers at the Boyce Thompson Institute (BTI) for Plant Research, advances the understanding of a disease mechanism common to plants, animals, and people.

That mechanism, called programmed cell death (PCD), causes a cell to commit suicide. PCD helps organisms contain infections, nip potential cancers in the bud, and get rid of old or unneeded cells. However, runaway PCD leads to everything from unseemly spots on tomatoes to Parkinson's and Alzheimer's diseases.

BTI Scientist and Cornell University Professor of Plant Pathology Gregory Martin studies the interaction of Pseudomonas syringae bacteria with plants to find what determines whether a host succumbs to disease. Martin and graduate student Robert Abramovitch previously found that AvrPtoB, a protein Pseudomonas injects into plants, disables PCD in a variety of susceptible plants and in yeast (a single-celled ancestor of both plants and animals). Abramovitch and Martin compared AvrPtoB's amino acid sequence to known proteins in other microbes and in higher organisms, but found no matches that might hint at how the protein works at the molecular level.

"We had some biochemical clues to what AvrPtoB was doing, but getting the three-dimensional crystal structure was really key," Martin explained. To find that structure, Martin and Abramovitch worked with collaborators at Rockefeller University. The structure of AvrPtoB revealed that the protein looks very much like a ubiquitin ligase, an enzyme plant and animal cells use to attach the small protein ubiquitin to unneeded or defective proteins. Other enzymes then chew up and "recycle" the ubiquitin-tagged proteins.

To confirm that AvrPtoB was a molecular mimic, Martin and Abramovitch altered parts of the protein that correspond to crucial sites on ubiquitin ligase. These changes rendered Pseudomonas harmless to susceptible tomato plants, and made the purified protein inactive. AvrPtoB's function is remarkable not only because its amino acid sequence is so different from other ubiquitin ligases, but also because bacteria don't use ubiquitin to recycle their own proteins.

"An interesting question is where this protein came from," Martin noted. "Did the bacteria steal it from a host and modify it over time, or did it evolve independently? We don't know."

Regardless, the discovery "helps us understand how organisms regulate cell death on a fundamental level," Martin said. AvrPtoB provides a sophisticated tool researchers can use to knock out PCD brought on by a variety of conditions, shedding light on immunity. The protein itself or a derivative might one day be applied to control disease in crops or in people. For now, Martin and Abramovitch are working to find which proteins AvrPtoB acts on, and what role those proteins play in host PCD.
-end-
Abramovitch and Martin collaborated with Radmila Janjusevic and C. Erec Stebbins of The Rockefeller University on this work. Funding came from a Burroughs-Welcome Investigators in Pathogenesis of Infectious Disease award, The Rockefeller University, a fellowship from the Natural Sciences and Engineering Research Council of Canada, the Triad Foundation, and the USDA National Research Initiative.

Boyce Thompson Institute

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