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dc.contributor.authorKaiserman, D
dc.contributor.authorBird, CH
dc.contributor.authorSun, J
dc.contributor.authorMatthews, A
dc.contributor.authorUng, K
dc.contributor.authorWhisstock, JC
dc.contributor.authorThompson, PE
dc.contributor.authorTrapani, JA
dc.contributor.authorBird, PI
dc.date.accessioned2020-12-22T03:19:44Z
dc.date.available2020-12-22T03:19:44Z
dc.date.issued2006-11-20
dc.identifierpii: jcb.200606073
dc.identifier.citationKaiserman, D., Bird, C. H., Sun, J., Matthews, A., Ung, K., Whisstock, J. C., Thompson, P. E., Trapani, J. A. & Bird, P. I. (2006). The major human and mouse granzymes are structurally and functionally divergent. JOURNAL OF CELL BIOLOGY, 175 (4), pp.619-630. https://doi.org/10.1083/jcb.200606073.
dc.identifier.issn0021-9525
dc.identifier.urihttp://hdl.handle.net/11343/257828
dc.description.abstractApproximately 2% of mammalian genes encode proteases. Comparative genomics reveals that those involved in immunity and reproduction show the most interspecies diversity and evidence of positive selection during evolution. This is particularly true of granzymes, the cytotoxic proteases of natural killer cells and CD8+ T cells. There are 5 granzyme genes in humans and 10 in mice, and it is suggested that granzymes evolve to meet species-specific immune challenge through gene duplication and more subtle alterations to substrate specificity. We show that mouse and human granzyme B have distinct structural and functional characteristics. Specifically, mouse granzyme B is 30 times less cytotoxic than human granzyme B and does not require Bid for killing but regains cytotoxicity on engineering of its active site cleft. We also show that mouse granzyme A is considerably more cytotoxic than human granzyme A. These results demonstrate that even "orthologous" granzymes have species-specific functions, having evolved in distinct environments that pose different challenges.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
dc.titleThe major human and mouse granzymes are structurally and functionally divergent
dc.typeJournal Article
dc.identifier.doi10.1083/jcb.200606073
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.source.titleThe Journal of Cell Biology
melbourne.source.volume175
melbourne.source.issue4
melbourne.source.pages619-630
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1179944
melbourne.contributor.authorTrapani, Joseph
dc.identifier.eissn1540-8140
melbourne.accessrightsOpen Access


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