Navigation Links
Pathogens use previously undescribed mechanism to sabotage host immune system

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
Cell Press

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:
(Date:11/18/2015)... , November 18, 2015 ... has published a new market report titled  Gesture Recognition ... and Forecast, 2015 - 2021. According to the report, the global ... and is anticipated to reach US$29.1 bn by 2021, ... North America dominated the ...
(Date:11/17/2015)... November 17, 2015 Paris ... 2015.  --> Paris , qui ... DERMALOG, le leader de l,innovation biométrique, a inventé ... passeports et empreintes sur la même surface de balayage. ... et l,autre pour les empreintes digitales. Désormais, un seul ...
(Date:11/17/2015)... SOUTH EASTON, Mass. , Nov. 17, 2015 /PRNewswire/ ... "Company"), a leader in the development and sale of ... to the worldwide life sciences industry, today announced it ... closing of its $5 million Private Placement (the "Offering"), ... Offering to $4,025,000.  One or more additional closings are ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... November 24, 2015 , ... ... the year and one of the premier annual events for pharmaceutical manufacturing: 2015 ... 8–11 November 2015, where ISPE hosted the largest number of attendees in more ...
(Date:11/24/2015)... 24, 2015  Clintrax Global, Inc., a worldwide provider of clinical ... today announced that the company has set a new quarterly earnings ... on quarter growth posted for Q3 of 2014 to Q3 of ... Mexico , with the establishment of an ... --> United Kingdom and Mexico ...
(Date:11/24/2015)... ... ... This fall, global software solutions leader SAP and AdVenture Capital brought together ... their BIG ideas to improve health and wellness in their schools. , Now, the ... title of SAP's Teen Innovator, an all-expenses paid trip to Super Bowl 50, and ...
(Date:11/24/2015)... Massachusetts , November 24, 2015 SHPG ... will participate in the Piper Jaffray 27 th Annual Healthcare ... Tuesday, December 1, 2015, at 8:30 a.m. EST (1:30 p.m. GMT). ... , Chief Financial Officer, will participate in the Piper Jaffray 27 ... , NY on Tuesday, December 1, 2015, at 8:30 a.m. ...
Breaking Biology Technology: