8G0P

Crystal structure of the human Ndc80:Nuf2 loop region

Summary for 8G0P

• Entry DOI: 10.2210/pdb8g0p/pdb
• Descriptor: Kinetochore protein NDC80 homolog, Kinetochore protein Nuf2 (3 entities in total)
• Functional Keywords: cell division, chromosome segregation, kinetochore, ndc80 complex, ndc80, nuf2, loop, hinge, human, cell cycle
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 28219.26

Authors

Zahm, J.A.,Jenni, S.,Harrison, S.C. (deposition date: 2023-02-01, release date: 2023-03-29, Last modification date: 2024-11-20)

Primary citation

Zahm, J.A.,Jenni, S.,Harrison, S.C.
Structure of the Ndc80 complex and its interactions at the yeast kinetochore-microtubule interface.
Open Biology, 13:220378-220378, 2023

PubMed Abstract: The conserved Ndc80 kinetochore complex, Ndc80c, is the principal link between mitotic spindle microtubules and centromere-associated proteins. We used AlphaFold 2 (AF2) to obtain predictions of the Ndc80 'loop' structure and of the Ndc80 : Nuf2 globular head domains that interact with the Dam1 subunit of the heterodecameric DASH/Dam1 complex (Dam1c). The predictions guided design of crystallizable constructs, with structures close to the predicted ones. The Ndc80 'loop' is a stiff, α-helical 'switchback' structure; AF2 predictions and positions of preferential cleavage sites indicate that flexibility within the long Ndc80c rod occurs instead at a hinge closer to the globular head. Conserved stretches of the Dam1 C terminus bind Ndc80c such that phosphorylation of Dam1 serine residues 257, 265 and 292 by the mitotic kinase Ipl1/Aurora B can release this contact during error correction of mis-attached kinetochores. We integrate the structural results presented here into our current molecular model of the kinetochore-microtubule interface. The model illustrates how multiple interactions between Ndc80c, DASH/Dam1c and the microtubule lattice stabilize kinetochore attachments.

PubMed: 36883282
DOI: 10.1098/rsob.220378

Experimental method

X-RAY DIFFRACTION (2 Å)