6EQT

CRYSTAL STRUCTURE OF THE HUMAN KINETOCHORE PROTEIN CENP-N

Summary for 6EQT

• Entry DOI: 10.2210/pdb6eqt/pdb
• Related: 6C0W
• EMDB information: 7326
• Descriptor: Centromere protein N (2 entities in total)
• Functional Keywords: dna-binding, pyrin domain, cenp-nl homology domain, related to iml3, dna binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: Q96H22
• Total number of polymer chains: 2
• Total formula weight: 52057.88

Authors

Pentakota, S.,Vetter, I.R.,Petrovic, A.,Musacchio, A. (deposition date: 2017-10-15, release date: 2018-01-17, Last modification date: 2024-05-08)

Primary citation

Pentakota, S.,Zhou, K.,Smith, C.,Maffini, S.,Petrovic, A.,Morgan, G.P.,Weir, J.R.,Vetter, I.R.,Musacchio, A.,Luger, K.
Decoding the centromeric nucleosome through CENP-N.
Elife, 6:-, 2017

PubMed Abstract: Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome. Here, we reveal the structural basis for the exquisite selectivity of CENP-N for centromeres. CENP-N uses charge and space complementarity to decode the L1 loop that is unique to CENP-A. It also engages in extensive interactions with a 15-base pair segment of the distorted nucleosomal DNA double helix, in a position predicted to exclude chromatin remodelling enzymes. Besides CENP-A, stable centromere recruitment of CENP-N requires a coincident interaction with a newly identified binding motif on nucleosome-bound CENP-C. Collectively, our studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly.

PubMed: 29280735
DOI: 10.7554/eLife.33442

Experimental method

X-RAY DIFFRACTION (2.735 Å)