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:6/30/2017)... Today, American Trucking Associations announced Seeing ... and eye tracking software, became the newest member ... "Artificial intelligence and advanced sensing algorithms ... driver,s attentiveness levels while on the road.  Drivers ... fatigue and prevent potential accidents, which could lead ...
(Date:5/16/2017)... , May 16, 2017  Veratad Technologies, LLC ( ... online age and identity verification solutions, announced today they ... Conference 2017, May 15 thru May 17, 2017, in ... and International Trade Center. Identity impacts ... and in today,s quickly evolving digital world, defining identity ...
(Date:4/19/2017)... April 19, 2017 The global ... landscape is marked by the presence of several large ... held by five major players - 3M Cogent, NEC ... accounted for nearly 61% of the global military biometric ... in the global military biometrics market boast global presence, ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... Proscia Inc ... hosting a Webinar titled, “Pathology is going digital. Is your lab ready?” with ... adoption best practices and how Proscia improves lab economics and realizes an increase ...
(Date:10/11/2017)... Bay, Florida (PRWEB) , ... October 11, 2017 ... ... and Drug Administration (FDA) has granted orphan drug designation to SBT-100, its novel ... (sdAb) for the treatment of osteosarcoma. SBT-100 is able to cross the cell ...
(Date:10/10/2017)... 10, 2017 International research firm Parks Associates announced ... at the TMA 2017 Annual Meeting , October 11 in ... residential home security market and how smart safety and security products impact ... Parks Associates: Smart Home ... "The residential security market has ...
(Date:10/9/2017)... FL (PRWEB) , ... October 09, 2017 , ... The ... scheduled to broadcast first quarter 2018. American Farmer airs Tuesdays at 8:30aET on RFD-TV. ... industry is faced with the challenge of how to continue to feed a growing ...
Breaking Biology Technology: