6eqt
From Proteopedia
CRYSTAL STRUCTURE OF THE HUMAN KINETOCHORE PROTEIN CENP-N
Structural highlights
Function[CENPN_HUMAN] Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPN is the first protein to bind specifically to CENPA nucleosomes and the direct binding of CENPA nucleosomes by CENPN is required for centromere assembly. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate.[1] [2] [3] [4] Publication Abstract from PubMedCentromere 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. Decoding the centromeric nucleosome through CENP-N.,Pentakota S, Zhou K, Smith C, Maffini S, Petrovic A, Morgan GP, Weir JR, Vetter IR, Musacchio A, Luger K Elife. 2017 Dec 27;6. doi: 10.7554/eLife.33442. PMID:29280735[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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