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-Structure paper
Title | Decoding the centromeric nucleosome through CENP-N. |
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Journal, issue, pages | Elife, Vol. 6, Year 2017 |
Publish date | Dec 27, 2017 |
Authors | Satyakrishna Pentakota / Keda Zhou / Charlotte Smith / Stefano Maffini / Arsen Petrovic / Garry P Morgan / John R Weir / Ingrid R Vetter / Andrea Musacchio / Karolin Luger / |
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 ...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. |
External links | Elife / PubMed:29280735 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.735 - 4.0 Å |
Structure data | EMDB-7326, PDB-6c0w: PDB-6eqt: |
Chemicals | ChemComp-HOH: |
Source |
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Keywords | STRUCTURAL PROTEIN/DNA / Nucleosome / CENP-A / kinetochore / CENP-N / STRUCTURAL PROTEIN-DNA complex / DNA BINDING PROTEIN / DNA-binding / pyrin domain / Cenp-NL homology domain / related to Iml3 |