7QRO

Crystal structure of the unconventional kinetochore protein Trypanosoma brucei KKT4 BRCT domain K543A mutant

Summary for 7QRO

• Entry DOI: 10.2210/pdb7qro/pdb
• Related: 6ZPK
• Descriptor: Trypanosoma brucei KKT4 463-645 K543A (2 entities in total)
• Functional Keywords: kinetochore, kinetoplastids, kkt4, brct, cell cycle
• Biological source: Trypanosoma brucei brucei
• Total number of polymer chains: 1
• Total formula weight: 19854.59

Authors

Ludzia, P.,Akiyoshi, B. (deposition date: 2022-01-11, release date: 2022-02-09, Last modification date: 2024-05-22)

Primary citation

Ludzia, P.,Hayashi, H.,Robinson, T.,Akiyoshi, B.,Redfield, C.
NMR study of the structure and dynamics of the BRCT domain from the kinetochore protein KKT4.
Biomol.Nmr Assign., 18:15-25, 2024

PubMed Abstract: KKT4 is a multi-domain kinetochore protein specific to kinetoplastids, such as Trypanosoma brucei. It lacks significant sequence similarity to known kinetochore proteins in other eukaryotes. Our recent X-ray structure of the C-terminal region of KKT4 shows that it has a tandem BRCT (BRCA1 C Terminus) domain fold with a sulfate ion bound in a typical binding site for a phosphorylated serine or threonine. Here we present the H, C and N resonance assignments for the BRCT domain of KKT4 (KKT4) from T. brucei. We show that the BRCT domain can bind phosphate ions in solution using residues involved in sulfate ion binding in the X-ray structure. We have used these assignments to characterise the secondary structure and backbone dynamics of the BRCT domain in solution. Mutating the residues involved in phosphate ion binding in T. brucei KKT4 BRCT results in growth defects confirming the importance of the BRCT phosphopeptide-binding activity in vivo. These results may facilitate rational drug design efforts in the future to combat diseases caused by kinetoplastid parasites.

PubMed: 38453826
DOI: 10.1007/s12104-024-10163-9

Experimental method

X-RAY DIFFRACTION (1.8 Å)