The study was published in an advance online edition of the Proceedings of the National Academy of Sciences during the week of April 9, 2007.

The study provides new evidence that Nod1, a member of the Nod-like Receptor (NLR) protein family, is activated by the protein SGT1, which also activates Resistance (R) proteins in plants; R proteins protect plants from various pathogens. The study also confirms structural similarities between the Nod1 protein, which plays a pivotal role in the innate immune systems recognition and response to bacterial infection and members of the R protein family.

"There has been a great deal of speculation that R proteins and Nod1 are related, but our study provides the first direct link between plants and humans," said Richard Ulevitch, the Scripps Research scientist whose laboratory conducted the study. "Plants have Nod-like receptors and similar immune responses to bacteria and other pathogens-the R proteins evolved to counteract these pathogenic effects. Our study provides a new perspective on the Nod1 pathway in mammalian cells as well as the value of drawing on plant studies of R protein pathways to better understand the pathogen recognition functions of these proteins."

The Nod proteins recognize invasive bacteria, specifically distinct substructures found in Gram-negative and Gram-positive organisms. Once activated, Nod1 produces a number of responses that include activation of intracellular signaling pathways, cytokine production and apoptosis or programmed cell death. Despite the fact that various models of Nod1 activation have been described, little has been known about other proteins that might affect the proteins activation. In contrast, a number of additional proteins have been linked to the activation pathways of the R protein in plants.

"The NLR family has clear links to human disease," Ulevitch said. "Out of the more than 20 proteins in the NLR family, several mutations are link
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Contact: Mike Benedyk
mbenedyk@scripps.edu
858-784-2052
Scripps Research Institute
9-Apr-2007