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dc.contributor.authorReyes-Turcu, FE
dc.contributor.authorShanks, JR
dc.contributor.authorKomander, D
dc.contributor.authorWilkinson, KD
dc.date.accessioned2018-08-30T13:40:43Z
dc.date.issued2008-07-11
dc.identifier28
dc.identifier.citationJOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 pp. 19581 - 19592
dc.identifier.issn0021-9258
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2438
dc.identifier.doi10.1074/jbc.M800947200
dc.description.abstractThe conjugation of polyubiquitin to target proteins acts as a signal that regulates target stability, localization, and function. Several ubiquitin binding domains have been described, and while much is known about ubiquitin binding to the isolated domains, little is known with regard to how the domains interact with polyubiquitin in the context of full-length proteins. Isopeptidase T(IsoT/USP5) is a deubiquitinating enzyme that is largely responsible for the disassembly of unanchored polyubiquitin in the cell. IsoT has four ubiquitin binding domains: a zinc finger domain (ZnF UBP), which binds the proximal ubiquitin, a UBP domain that forms the active site, and two ubiquitin-associated (UBA) domains whose roles are unknown. Here, we show that the UBA domains are involved in binding two different polyubiquitin isoforms, linear and K48-linked. Using isothermal titration calorimetry, we show that IsoT has at least four ubiquitin binding sites for both polyubiquitin isoforms. The thermodynamics of the interactions reveal that the binding is enthalpy-driven. Mutation of the UBA domains suggests that UBA1 and UBA2 domains of IsoT interact with the third and fourth ubiquitins in both polyubiquitin isoforms, respectively. These data suggest that recognition of the polyubiquitin isoforms by IsoT involves considerable conformational mobility in the polyubiquitin ligand, in the enzyme, or in both.
dc.format.extent19581 - 19592
dc.languageeng
dc.language.isoeng
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.titleRecognition of polyubiquitin isoforms by the multiple ubiquitin binding modules of isopeptidase T
dc.typeJournal Article
rioxxterms.versionofrecord10.1074/jbc.M800947200
rioxxterms.licenseref.startdate2008-07-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJOURNAL OF BIOLOGICAL CHEMISTRY
pubs.notesaffiliation: Wilkinson, KD (Reprint Author), Emory Univ, Sch Med, Dept Biochem, 4017 Rollins Res Bldg,1510 Clifton Rd, Atlanta, GA 30322 USA. Reyes-Turcu, Francisca E.; Shanks, John R.; Wilkinson, Keith D., Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA. Komander, David, Inst Canc Res, London SW3 6JB, England. keywords-plus: UBA DOMAIN; DEUBIQUITINATING ENZYME; STRUCTURAL BASIS; CRYSTAL-STRUCTURE; PROTEIN; CHAINS; COMPLEX; FAMILY; TETRAUBIQUITIN; MONOUBIQUITIN research-areas: Biochemistry & Molecular Biology web-of-science-categories: Biochemistry & Molecular Biology author-email: [email protected] funding-acknowledgement: NIGMS NIH HHS [GM075426, GM30308] number-of-cited-references: 55 times-cited: 76 usage-count-last-180-days: 1 usage-count-since-2013: 16 journal-iso: J. Biol. Chem. doc-delivery-number: 322PK unique-id: ISI:000257387600044 oa: gold_or_bronze da: 2018-08-30
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.volume283
pubs.embargo.termsNot known
dc.contributor.icrauthorKomander, Daviden


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