8OWI

Crystal structure of the corona-targeting domain of CENP-E

Summary for 8OWI

• Entry DOI: 10.2210/pdb8owi/pdb
• Descriptor: Centromere-associated protein E (2 entities in total)
• Functional Keywords: kinesin motor, kinetochores, microtubules, mitosis, cell cycle
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 34777.82

Authors

Legal, T.,Davies, O.R.,Welburn, J.P.I. (deposition date: 2023-04-28, release date: 2023-06-21, Last modification date: 2024-07-03)

Primary citation

Weber, J.,Legal, T.,Lezcano, A.P.,Gluszek-Kustusz, A.,Paterson, C.,Eibes, S.,Barisic, M.,Davies, O.R.,Welburn, J.P.I.
A conserved CENP-E region mediates BubR1-independent recruitment to the outer corona at mitotic onset.
Curr.Biol., 34:1133-1141.e4, 2024

PubMed Abstract: The outer corona plays an essential role at the onset of mitosis by expanding to maximize microtubule attachment to kinetochores. The low-density structure of the corona forms through the expansion of unattached kinetochores. It comprises the RZZ complex, the dynein adaptor Spindly, the plus-end directed microtubule motor centromere protein E (CENP-E), and the Mad1/Mad2 spindle-assembly checkpoint proteins. CENP-E specifically associates with unattached kinetochores to facilitate chromosome congression, interacting with BubR1 at the kinetochore through its C-terminal region (2091-2358). We recently showed that CENP-E recruitment to BubR1 at the kinetochores is both rapid and essential for correct chromosome alignment. However, CENP-E is also recruited to the outer corona by a second, slower pathway that is currently undefined. Here, we show that BubR1-independent localization of CENP-E is mediated by a conserved loop that is essential for outer-corona targeting. We provide a structural model of the entire CENP-E kinetochore-targeting domain combining X-ray crystallography and Alphafold2. We reveal that maximal recruitment of CENP-E to unattached kinetochores critically depends on BubR1 and the outer corona, including dynein. Ectopic expression of the CENP-E C-terminal domain recruits the RZZ complex, Mad1, and Spindly, and prevents kinetochore biorientation in cells. We propose that BubR1-recruited CENP-E, in addition to its essential role in chromosome alignment to the metaphase plate, contributes to the recruitment of outer corona proteins through interactions with the CENP-E corona-targeting domain to facilitate the rapid capture of microtubules for efficient chromosome alignment and mitotic progression.

PubMed: 38354735
DOI: 10.1016/j.cub.2024.01.042

Experimental method

X-RAY DIFFRACTION (2.14 Å)