5Z08

The crystal structure of kinetochore subunits Cenp-H/I/K triple complex

Summary for 5Z08

• Entry DOI: 10.2210/pdb5z08/pdb
• Descriptor: Cenp-I, Cenp-K, Cenp-H, ... (4 entities in total)
• Functional Keywords: protein complex, kinetochore, centromere, cell cycle
• Biological source: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719); More
• Total number of polymer chains: 4
• Total formula weight: 75652.91

Authors

Tian, W.,Hu, L.Q.,He, X. (deposition date: 2017-12-18, release date: 2018-10-31, Last modification date: 2024-03-27)

Primary citation

Hu, L.,Huang, H.,Hei, M.,Yang, Y.,Li, S.,Liu, Y.,Dou, Z.,Wu, M.,Li, J.,Wang, G.Z.,Yao, X.,Liu, H.,He, X.,Tian, W.
Structural analysis of fungal CENP-H/I/K homologs reveals a conserved assembly mechanism underlying proper chromosome alignment.
Nucleic Acids Res., 47:468-479, 2019

PubMed Abstract: The kinetochore is a proteinaceous complex that is essential for proper chromosome segregation. As a core member of the inner kinetochore, defects of each subunit in the CENP-H/I/K complex cause dysfunction of kinetochore that leads to chromosome mis-segregation and cell death. However, how the CENP-H/I/K complex assembles and promotes kinetochore function are poorly understood. We here determined the crystal structures of CENP-I N-terminus alone from Chaetomium thermophilum and its complex with CENP-H/K from Thielavia terrestris, and verified the identified interactions. The structures and biochemical analyses show that CENP-H and CENP-K form a heterodimer through both N- and C-terminal interactions. CENP-I integrates into the CENP-H/K complex by binding to the C-terminus of CENP-H, leading to formation of the ternary complex in which CENP-H is sandwiched between CENP-K and CENP-I. Our sequence comparisons and mutational analyses showed that this architecture of the CENP-H/I/K complex is conserved in human. Mutating the binding interfaces of CENP-H for either CENP-K or CENP-I significantly reduced their localizations at centromeres and induced massive chromosome alignment defects during mitosis, suggesting that the identified interactions are critical for CENP-H/I/K complex assembly at the centromere and kinetochore function. Altogether, our findings unveil the evolutionarily conserved assembly mechanism of the CENP-H/I/K complex that is critical for proper chromosome alignment.

PubMed: 30407575
DOI: 10.1093/nar/gky1108

Experimental method

X-RAY DIFFRACTION (2.199 Å)