Biochemical Characterization of the Activity and Specificity of ULP1 Family Members

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dc.contributor Orth , Kim
dc.date 2010 -07 -12T18 :08 :44Z
dc.date 2010 -07 -12T18 :08 :44Z
dc.date 2006 -05 -15
dc.date.accessioned 2013 -04 -17T19 :02 :17Z
dc.date.available 2013 -04 -17T19 :02 :17Z
dc.date.issued 2013 -04 -17
dc.identifier
dc.identifier http : / /hdl .handle .net /2152 .5 /461
dc.identifier.uri http : / /hdl .handle .net /2152 .5 /461
dc.description The reversible posttranslational modification , SUMO , modulates the activity of a diverse set of target proteins . Conjugation machinery charges the processed -SUMO so that it can be linked via an isopeptide bond to a target protein . The removal of SUMO moieties from conjugated proteins by isopeptidases regenerates pools of processed -SUMOs and unmodified target proteins . Yeast Ulp1 is the founding member of a growing family of these isopeptidases , or deSUMOylating enzymes . Another Ulp1 , XopD from Xanthomonas campestris pv . vesicatoria , is expressed as a secreted virulence factor by this plant bacterial pathogen . In vitro peptidase assays were performed to characterize the activity of XopD and showed that XopD can process plant SUMOs , but is unable to process mammalian SUMOs . Enzymatic studies further demonstrated that XopD functions as a cysteine protease . Isopeptide bond cleavage was demonstrated by the ability of XopD to cleave the plant SUMO moiety from in vitro SUMOylated RanGAP . These studies showed that XopD has a rigid SUMO substrate specificity in contrast to yeast Ulp1 , which is a more promiscuous protease in its choice of SUMO substrate . To further investigate the SUMO substrate specificity of XopD the crystal structures of the catalytic core of XopD and XopD C470A were determined . Although the catalytic core residues align between the XopD and Ulp1 structures , there are apparent structural differences that may account for the differences in choice of SUMO substrate . Mutational studies on tomato SUMO and yeast Smt3 identified some key residues in the enzyme -substrate recognition , but ultimately showed that there are many regions in the SUMO proteins that are accounting for the enzyme's ability to recognize certain substrates . Experiments with the Arabidopsis thaliana family of SUMOs and ULP1s identified varying specificity of the AtULP1s . The evolutionarily conserved SUMO conjugating proteins , E1 and E2 , recognize a diverse set of AtSUMO proteins using them to modify protein substrates . By contrast , the deSUMOylating enzymes differentially recognize the Arabidopsis SUMO proteins , resulting in specificity of the de -conjugating machinery . Therefore , the SUMO proteins in this signaling system have evolved to contain information that allows for both redundancy with the conjugation system and the diversity with deconjugating enzymes .
dc.format Electronic
dc.format application /pdf
dc.format born digital
dc.language en
dc.subject Endopeptidases
dc.subject SUMO Proteins
dc.subject Cysteine Endopeptidases
dc.title Biochemical Characterization of the Activity and Specificity of ULP1 Family Members
dc.type Text
dc.type dissertation

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Biochemical Characterization of the Activity and Specificity of ULP1 Family Members. Available electronically from http : / /hdl .handle .net /2152 .5 /461 .

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