Navigation Links
Pathogens use previously undescribed mechanism to sabotage host immune system
Date:12/7/2007

New research identifies a previously unknown enzymatic mechanism that subverts the early host immune response and promotes pathogenicity by manipulating a common signaling pathway in host cells. The research, published by Cell Press in the December 14th issue of Molecular Cell, may have important implications for the food industry and for development of new antibiotics. In addition, the results lead to intriguing questions about whether mammalian cells can make use of a similar mechanism for potentially permanent and irreversible posttranslational modifications.

Many gram-negative bacterial pathogens have evolved specialized mechanisms for disrupting the ability of host cells to activate innate immune responses that will provide immediate defense against infection. Mitogen-activated protein kinase (MAPK) pathways play key roles in activating host innate immune responses and are frequent targets of pathogenic effectors in both plants and animal systems. All MAPKs contain a threonine -X-tyrosine motif and require phosphorylation of both threonine and tyrosine for activation. Previous work demonstrated that members of the OspF family, including OspF from Shigella and SpvC from Salmonella, are phosphothreonine lyases that promote pathogenicity by directly targeting and irreversibly inhibiting the activation of MAPKs.

Dr. Feng Shao from the National Institute of Biological Sciences, Beijing and colleagues used mass spectrometry to examine the mechanism underlying inactivation of MAPKs by the OspF family of effectors. The researchers determined the crystal structure of SpvC and its complex with a phosphopeptide substrate. The enzyme-substrate complex revealed how SpvC docks with activated MAPK by recognizing the phosphotyrosine and then maneuvers the phosphothreonine into the enzyme active site. These data implicated the MAPK p38 as the likely preferred substrate for OspF and SpvC during bacterial infection because it has the required conformational flexibility for this interaction. The researchers went on to identify a previously unknown catalytic mechanism of acid-base mediated "-elimination of phosphoserine/phosphothreonine that irreversibly inactivated the kinase.

Our data provide biochemical and structural evidence for specific recognition of the dual phosphorylated MAPK substrates by the OspF family of phosphothreonine lyases and explain the enzymes differential activities towards different MAPK substrates, explains Dr. Shao. Further, as phosphorylation of serine and threonine residues is widely used as a regulatory mechanism in mammalian cells, the researchers speculated that phosphoserine or phosphothreonine lyases might exist in eukaryotes and serve as post-translational modification enzymes that irreversible dephosphorylate kinases or other phosphorylated substrates.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related biology news :

1. Understanding, combating foodborne pathogens E. coli 0157 and salmonella
2. New magnetic separation technique might detect multiple pathogens at once
3. New system would use rotating magnetic field to detect pathogens
4. K-State specialist in tick-borne pathogens receives $1.8 million grant
5. Baiji Dolphin previously thought extinct spotted in the Yangtze River
6. Carnegie Mellon scientists investigate initial molecular mechanism that triggers neuronal firing
7. Scientists find clue to mechanisms of gene signaling and regulation
8. Neural stem cell study reveals mechanism that may play role in cancer
9. New insight into the mechanisms of voltage sensing and transduction in biological processes
10. Mechanism for the in-vivo transport of siRNA
11. Scientists decipher mechanism behind antimicrobial hole punchers
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/18/2017)... -- Socionext Inc., a global expert in SoC-based imaging and computing solutions, ... which features the company,s hybrid codec technology. A demonstration utilizing TeraFaces ... will be showcased during the upcoming Medtec Japan at Tokyo Big ... Las Vegas Convention Center April 24-27. ... Click here for an image of ...
(Date:4/11/2017)... -- Research and Markets has announced the addition of ... offering. ... market to grow at a CAGR of 30.37% during the period ... has been prepared based on an in-depth market analysis with inputs ... growth prospects over the coming years. The report also includes a ...
(Date:4/5/2017)... -- Today HYPR Corp. , leading innovator in ... the HYPR platform is officially FIDO® Certified . ... that empowers biometric authentication across Fortune 500 enterprises and ... 15 million users across the financial services industry, however ... suites and physical access represent a growing portion of ...
Breaking Biology News(10 mins):
(Date:6/23/2017)... ... June 23, 2017 , ... ... announced the latest version of LimitLIS®, its rapidly growing Laboratory Information System. , ... user adoption, ensure installation integrity, and provide more customization options. Each of these ...
(Date:6/23/2017)... ... June 23, 2017 , ... The Academy of ... the University Aviation Association (UAA), the unifying voice for collegiate aviation education, are ... encourage teamwork, competition, and success through a STEM-based education platform. , Much like ...
(Date:6/22/2017)... (PRWEB) , ... June 21, 2017 , ... Building on ... more inspiring, and more informative on the very latest developments in radical life extension. ... fun of a festival, and the empowerment of personal development, making it the largest ...
(Date:6/22/2017)... ... June 22, 2017 , ... For the months of May ... Spotlight series on “Cell Therapy Regulation” for its regenerative medicine followship. ... the unique regulatory challenges of stem cell medical research. , Stem cell clinical ...
Breaking Biology Technology: