Kinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domains

DOI: 10.1083/jcb.202101022

Authors: Gabriele Marciano (University of Oxford) , Midori Ishii (University of Oxford) , Olga O. Nerusheva (University of Oxford) , Bungo Akiyoshi (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Cell Biology , VOL 220

State: Published (Approved)
Published: August 2021
Diamond Proposal Number(s): 18069

Abstract: 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.

Journal Keywords: Cell cycle and division; Genetics; Structural Biology

Diamond Keywords: Sleeping Sickness

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Added On: 09/06/2021 10:03

Documents:
jcb_202101022.pdf

Discipline Tags:

Infectious Diseases Disease in the Developing World Health & Wellbeing Biochemistry Genetics Chemistry Structural biology Life Sciences & Biotech Parasitology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)