7qoo

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Structure of the human inner kinetochore CCAN complex

Structural highlights

7qoo is a 10 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:	Electron Microscopy, Resolution 4.6Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CENPK_HUMAN Chromosomal aberrations involving CENPK are a cause of acute leukemias. Translocation t(5;11)(q12;q23) with KMT2A/MLL1.^[1]

Function

CENPK_HUMAN Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. Acts in coordination with KNL1 to recruit the NDC80 complex to the outer kinetochore.^[2] ^[3] ^[4]

Publication Abstract from PubMed

Centromeres are specialized chromosome loci that seed the kinetochore, a large protein complex that effects chromosome segregation. A 16-subunit complex, the constitutive centromere associated network (CCAN), connects between the specialized centromeric chromatin, marked by the histone H3 variant CENP-A, and the spindle-binding moiety of the kinetochore. Here, we report a cryo-electron microscopy structure of human CCAN. We highlight unique features such as the pseudo GTPase CENP-M and report how a crucial CENP-C motif binds the CENP-LN complex. The CCAN structure has implications for the mechanism of specific recognition of the CENP-A nucleosome. A model consistent with our structure depicts the CENP-C-bound nucleosome as connected to the CCAN through extended, flexible regions of CENP-C. An alternative model identifies both CENP-C and CENP-N as specificity determinants but requires CENP-N to bind CENP-A in a mode distinct from the classical nucleosome octamer.

Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization.,Pesenti ME, Raisch T, Conti D, Walstein K, Hoffmann I, Vogt D, Prumbaum D, Vetter IR, Raunser S, Musacchio A Mol Cell. 2022 Jun 2;82(11):2113-2131.e8. doi: 10.1016/j.molcel.2022.04.027. Epub , 2022 May 6. PMID:35525244^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Taki T, Hayashi Y, Taniwaki M, Seto M, Ueda R, Hanada R, Suzukawa K, Yokota J, Morishita K. Fusion of the MLL gene with two different genes, AF-6 and AF-5alpha, by a complex translocation involving chromosomes 5, 6, 8 and 11 in infant leukemia. Oncogene. 1996 Nov 21;13(10):2121-30 PMID:8950979
↑ Okada M, Cheeseman IM, Hori T, Okawa K, McLeod IX, Yates JR 3rd, Desai A, Fukagawa T. The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres. Nat Cell Biol. 2006 May;8(5):446-57. Epub 2006 Apr 16. PMID:16622420 doi:http://dx.doi.org/ncb1396
↑ 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
↑ Cheeseman IM, Hori T, Fukagawa T, Desai A. KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates. Mol Biol Cell. 2008 Feb;19(2):587-94. Epub 2007 Nov 28. PMID:18045986 doi:http://dx.doi.org/10.1091/mbc.E07-10-1051
↑ Pesenti ME, Raisch T, Conti D, Walstein K, Hoffmann I, Vogt D, Prumbaum D, Vetter IR, Raunser S, Musacchio A. Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization. Mol Cell. 2022 Jun 2;82(11):2113-2131.e8. PMID:35525244 doi:10.1016/j.molcel.2022.04.027