Kinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domainsation domains
The kinetochore is the macromolecular protein complex that assembles onto centromeric DNA and binds spindle microtubules. Evolutionarily divergent kinetoplastids have an unconventional set of kinetochore proteins. It remains unknown how kinetochores assemble at centromeres in these organisms. Here,...
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| Fformat: | Journal article |
| Iaith: | English |
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Rockefeller University Press
2021
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| _version_ | 1826276704274874368 |
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| author | Marcianò, G Ishii, M Nerusheva, OO Akiyoshi, B |
| author_facet | Marcianò, G Ishii, M Nerusheva, OO Akiyoshi, B |
| author_sort | Marcianò, G |
| collection | OXFORD |
| description | The kinetochore is the macromolecular protein complex that assembles onto centromeric DNA and binds spindle microtubules. Evolutionarily divergent kinetoplastids have an unconventional set of kinetochore proteins. It remains unknown how kinetochores assemble at centromeres in these organisms. Here, we characterize KKT2 and KKT3 in the kinetoplastid parasite Trypanosoma brucei. In addition to the N-terminal kinase domain and C-terminal divergent polo boxes, these proteins have a central domain of unknown function. We show that KKT2 and KKT3 are important for the localization of several kinetochore proteins and that their central domains are sufficient for centromere localization. Crystal structures of the KKT2 central domain from two divergent kinetoplastids reveal a unique zinc-binding domain (termed the CL domain for centromere localization), which promotes its kinetochore localization in T. brucei. Mutations in the equivalent domain in KKT3 abolish its kinetochore localization and function. Our work shows that the unique central domains play a critical role in mediating the centromere localization of KKT2 and KKT3. |
| first_indexed | 2024-03-06T23:17:54Z |
| format | Journal article |
| id | oxford-uuid:67bfe1de-64de-4180-88b3-b199c1b386fa |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:17:54Z |
| publishDate | 2021 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | oxford-uuid:67bfe1de-64de-4180-88b3-b199c1b386fa2022-03-26T18:40:21ZKinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domainsation domainsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:67bfe1de-64de-4180-88b3-b199c1b386faEnglishSymplectic ElementsRockefeller University Press2021Marcianò, GIshii, MNerusheva, OOAkiyoshi, BThe kinetochore is the macromolecular protein complex that assembles onto centromeric DNA and binds spindle microtubules. Evolutionarily divergent kinetoplastids have an unconventional set of kinetochore proteins. It remains unknown how kinetochores assemble at centromeres in these organisms. Here, we characterize KKT2 and KKT3 in the kinetoplastid parasite Trypanosoma brucei. In addition to the N-terminal kinase domain and C-terminal divergent polo boxes, these proteins have a central domain of unknown function. We show that KKT2 and KKT3 are important for the localization of several kinetochore proteins and that their central domains are sufficient for centromere localization. Crystal structures of the KKT2 central domain from two divergent kinetoplastids reveal a unique zinc-binding domain (termed the CL domain for centromere localization), which promotes its kinetochore localization in T. brucei. Mutations in the equivalent domain in KKT3 abolish its kinetochore localization and function. Our work shows that the unique central domains play a critical role in mediating the centromere localization of KKT2 and KKT3. |
| spellingShingle | Marcianò, G Ishii, M Nerusheva, OO Akiyoshi, B Kinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domainsation domains |
| title | Kinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domainsation domains |
| title_full | Kinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domainsation domains |
| title_fullStr | Kinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domainsation domains |
| title_full_unstemmed | Kinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domainsation domains |
| title_short | Kinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domainsation domains |
| title_sort | kinetoplastid kinetochore proteins kkt2 and kkt3 have unique centromere localization domainsation domains |
| work_keys_str_mv | AT marcianog kinetoplastidkinetochoreproteinskkt2andkkt3haveuniquecentromerelocalizationdomainsationdomains AT ishiim kinetoplastidkinetochoreproteinskkt2andkkt3haveuniquecentromerelocalizationdomainsationdomains AT nerushevaoo kinetoplastidkinetochoreproteinskkt2andkkt3haveuniquecentromerelocalizationdomainsationdomains AT akiyoshib kinetoplastidkinetochoreproteinskkt2andkkt3haveuniquecentromerelocalizationdomainsationdomains |