Biochemical Characterization of the Yersinia Effector Protein, Yopjbiochemical Characterization of the Yersinia

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Title: Biochemical Characterization of the Yersinia Effector Protein, Yopjbiochemical Characterization of the Yersinia
Author: Mukherjee, Sohini
Abstract: Yersinia species , the causal agent of plague and gastroenteritis , uses a variety of type III effector proteins to target eukaryotic signaling systems . The effector YopJ disrupts the mitogen -activated protein kinase and the nuclear factor κ B signaling pathways used in innate immune response by preventing activation of the family of mitogen -activated protein kinase kinases . The catalytic domain of YopJ is similar to Clan CE of cysteine proteases , and mutating the putative catalytic cysteine disrupts YopJ's inhibitory activity . YopJ binds mitogenactivated protein kinase kinases , including MKK1 through MKK6 , and the related kinase , IκB kinase beta , however , the mechanism by which this binding leads to inactivation of these kinases is unknown . An in vitro cell -free signaling system was developed to recapitulate the inhibition of eukaryotic signaling by YopJ . Mass spectrometric studies were undertaken to determine the biochemical nature of modification of the mitogen -activated protein kinase kinases in the presence of YopJ . Based on the observations , a simple , molecular mechanism utilized by YopJ to block the signaling pathways was discovered . YopJ acted as an acetyltransferase , using acetyl coenzyme A , to modify the critical serine and threonine residues in the activation loop of mitogen -activated protein kinase kinases and thereby blocking phosphorylation . The acetylation on the kinase directly competed with phosphorylation , preventing activation of the modified protein . An essential characteristic feature of bacterial effector proteins is that they usurp or mimic a eukaryotic activity and refine this activity to produce an extremely efficient mechanism to combat eukaryotic signaling . Therefore , modification of amino acids , other than lysine , by acetylation could be a commonly used eukaryotic mechanism that has been undetected previously . The acetylation of these amino acids may compete with various other types of posttranslational modifications , such as ubiquitination , SUMOylation and glycosylation . Several questions that still need to be addressed are : Is this modification reversible ? What are the eukaryotic proteins that add and remove this type of posttranslational modification ? How do bacterial effectors use this activity ? The characterization of a bacterial effector as a serine or threonine acetyltransferase presents a previously unknown paradigm to be considered for other biological signaling pathways .
URI: http : / /hdl .handle .net /2152 .5 /254
Date: 2007-05-22

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Biochemical Characterization of the Yersinia Effector Protein, Yopjbiochemical Characterization of the Yersinia. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /254 .

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