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Structural characterization of KKT4, an unconventional microtubule-binding kinetochore protein

DOI: 10.1016/j.str.2021.04.004 DOI Help

Authors: Patryk Ludzia (University of Oxford) , Edward D. Lowe (University of Oxford) , Gabriele Marcianò (University of Oxford) , Shabaz Mohammed (University of Oxford) , Christina Redfield (University of Oxford) , Bungo Akiyoshi (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 5

State: Published (Approved)
Published: April 2021
Diamond Proposal Number(s): 23459

Open Access Open Access

Abstract: The kinetochore is the macromolecular machinery that drives chromosome segregation by interacting with spindle microtubules. Kinetoplastids (such as Trypanosoma brucei), a group of evolutionarily divergent eukaryotes, have a unique set of kinetochore proteins that lack any significant homology to canonical kinetochore components. To date, KKT4 is the only kinetoplastid kinetochore protein that is known to bind microtubules. Here we use X-ray crystallography, NMR spectroscopy, and crosslinking mass spectrometry to characterize the structure and dynamics of KKT4. We show that its microtubule-binding domain consists of a coiled-coil structure followed by a positively charged disordered tail. The structure of the C-terminal BRCT domain of KKT4 reveals that it is likely a phosphorylation-dependent protein-protein interaction domain. The BRCT domain interacts with the N-terminal region of the KKT4 microtubule-binding domain and with a phosphopeptide derived from KKT8. Taken together, these results provide structural insights into the unconventional kinetoplastid kinetochore protein KKT4.

Journal Keywords: kinetochore; kinetoplastid; Trypanosoma brucei; KKT4; microtubules; X-ray crystallography; NMR spectroscopy; crosslinking mass spectrometry; BRCT domain; coiled coil

Diamond Keywords: Sleeping Sickness

Subject Areas: Biology and Bio-materials, Chemistry


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

Added On: 05/05/2021 09:35

Documents:
1-s2.0-S0969212621001209-main.pdf

Discipline Tags:

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

Technical Tags:

Diffraction Macromolecular Crystallography (MX)