6eqt

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CRYSTAL STRUCTURE OF THE HUMAN KINETOCHORE PROTEIN CENP-NCRYSTAL STRUCTURE OF THE HUMAN KINETOCHORE PROTEIN CENP-N

Structural highlights

6eqt is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.735Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

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.

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.

See Also

References

  1. Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR 3rd, Cleveland DW. The human CENP-A centromeric nucleosome-associated complex. Nat Cell Biol. 2006 May;8(5):458-69. Epub 2006 Apr 16. PMID:16622419 doi:http://dx.doi.org/ncb1397
  2. Izuta H, Ikeno M, Suzuki N, Tomonaga T, Nozaki N, Obuse C, Kisu Y, Goshima N, Nomura F, Nomura N, Yoda K. Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells. Genes Cells. 2006 Jun;11(6):673-84. PMID:16716197 doi:http://dx.doi.org/GTC969
  3. McClelland SE, Borusu S, Amaro AC, Winter JR, Belwal M, McAinsh AD, Meraldi P. The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity. EMBO J. 2007 Dec 12;26(24):5033-47. doi: 10.1038/sj.emboj.7601927. Epub 2007 Nov , 15. PMID:18007590 doi:http://dx.doi.org/10.1038/sj.emboj.7601927
  4. Carroll CW, Silva MC, Godek KM, Jansen LE, Straight AF. Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N. Nat Cell Biol. 2009 Jul;11(7):896-902. doi: 10.1038/ncb1899. Epub 2009 Jun 21. PMID:19543270 doi:http://dx.doi.org/10.1038/ncb1899
  5. Pentakota S, Zhou K, Smith C, Maffini S, Petrovic A, Morgan GP, Weir JR, Vetter IR, Musacchio A, Luger K. Decoding the centromeric nucleosome through CENP-N. Elife. 2017 Dec 27;6. doi: 10.7554/eLife.33442. PMID:29280735 doi:http://dx.doi.org/10.7554/eLife.33442

6eqt, resolution 2.73Å

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