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  • Cell & molecular biology

Published online: 10 January 2008 | doi:10.1038/nchina.2008.5

Bacterial pathogens: How they work

Felix Cheung

Introduction

© (2007) Nature Structural & Molecular Biology

Salmonella is a major cause of food poisoning. The bacteria use the virulence protein, SpvC, to interfere with the human immune system by removing the phosphate groups of phosphothreonine antibodies in mitogen-activated protein kinase (MAPK) signalling pathways. Jijie Chai at the National Institute of Biological Sciences in Beijing and co-workers¹ have solved the structure of SpvC and shown how different interaction sites in the protein provide its virulence activity.

The researchers studied the structure of SpvC in its free form and the form it takes when bound to a substrate comprised of a doubly phosphorylated human ERK2 MAPK peptide (see image). The two phosphorylated residues of the peptide, namely pThr183 and pTyr185, formed the main contacts between the peptide and SpvC.

The researchers found that SpvC from Salmonella and other members of the phosphothreonine lyase family, such as YopJ of Yersinia and OspF of Shigella, all contain this pThr–peptide–pTyr motif. They also found that pThr183 became hydrophobic when SpvC was in its substrate-bound form, thereby creating a water-proof environment and allowing other interaction sites in the protein to attack the phosphate group more quickly.

This finding fits together part of the puzzle of how Salmonella interferes with the human immune system. Knowing the structure of the SpvC will help scientists design better drugs to fight Salmonella and related bacteria.

The authors of this work are from:
Graduate Program in Chinese Academy of Medical Sciences and Beijing Union Medical College, Beijing, China; National Institute of Biological Sciences, Beijing, China; State Key Lab of Microbial Technology, Shandong University, Jinan, China; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA.

Reference

1. Chen, L.et al. Structural basis for the catalytic mechanism of phosphothreonine lyase. Nature Struct. Mol. Biol. doi: 10.1038/nsmb1329 (2007). | Article |