7xho

Structure of human inner kinetochore CCAN complexStructure of human inner kinetochore CCAN complex

Structural highlights

7xho 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 3.29Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CENPH_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. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate.^[1] ^[2] ^[3]

Publication Abstract from PubMed

In mitosis, accurate chromosome segregation depends on kinetochores that connect centromeric chromatin to spindle microtubules. The centromeres of budding yeast, which are relatively simple, are connected to individual microtubules via a kinetochore constitutive centromere associated network (CCAN). However, the complex centromeres of human chromosomes comprise millions of DNA base pairs and attach to multiple microtubules. Here, by use of cryo-electron microscopy and functional analyses, we reveal the molecular basis of how human CCAN interacts with duplex DNA and facilitates accurate chromosome segregation. The overall structure relates to the cooperative interactions and interdependency of the constituent sub-complexes of the CCAN. The duplex DNA is topologically entrapped by human CCAN. Further, CENP-N does not bind to the RG-loop of CENP-A but to DNA in the CCAN complex. The DNA binding activity is essential for CENP-LN localization to centromere and chromosome segregation during mitosis. Thus, these analyses provide new insights into mechanisms of action underlying kinetochore assembly and function in mitosis.

Structural insights into human CCAN complex assembled onto DNA.,Tian T, Chen L, Dou Z, Yang Z, Gao X, Yuan X, Wang C, Liu R, Shen Z, Gui P, Teng M, Meng X, Hill DL, Li L, Zhang X, Liu X, Sun L, Zang J, Yao X Cell Discov. 2022 Sep 9;8(1):90. doi: 10.1038/s41421-022-00439-6. PMID:36085283^[4]

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

References

↑ Saffery R, Sumer H, Hassan S, Wong LH, Craig JM, Todokoro K, Anderson M, Stafford A, Choo KH. Transcription within a functional human centromere. Mol Cell. 2003 Aug;12(2):509-16. PMID:14536089 doi:10.1016/s1097-2765(03)00279-x
↑ Orthaus S, Ohndorf S, Diekmann S. RNAi knockdown of human kinetochore protein CENP-H. Biochem Biophys Res Commun. 2006 Sep 15;348(1):36-46. PMID:16875666 doi:10.1016/j.bbrc.2006.06.187
↑ 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
↑ Tian T, Chen L, Dou Z, Yang Z, Gao X, Yuan X, Wang C, Liu R, Shen Z, Gui P, Teng M, Meng X, Hill DL, Li L, Zhang X, Liu X, Sun L, Zang J, Yao X. Structural insights into human CCAN complex assembled onto DNA. Cell Discov. 2022 Sep 9;8(1):90. doi: 10.1038/s41421-022-00439-6. PMID:36085283 doi:http://dx.doi.org/10.1038/s41421-022-00439-6

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OCA

[1] Saffery R, Sumer H, Hassan S, Wong LH, Craig JM, Todokoro K, Anderson M, Stafford A, Choo KH. Transcription within a functional human centromere. Mol Cell. 2003 Aug;12(2):509-16. PMID:14536089 doi:10.1016/s1097-2765(03)00279-x

[2] Orthaus S, Ohndorf S, Diekmann S. RNAi knockdown of human kinetochore protein CENP-H. Biochem Biophys Res Commun. 2006 Sep 15;348(1):36-46. PMID:16875666 doi:10.1016/j.bbrc.2006.06.187

[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] Tian T, Chen L, Dou Z, Yang Z, Gao X, Yuan X, Wang C, Liu R, Shen Z, Gui P, Teng M, Meng X, Hill DL, Li L, Zhang X, Liu X, Sun L, Zang J, Yao X. Structural insights into human CCAN complex assembled onto DNA. Cell Discov. 2022 Sep 9;8(1):90. doi: 10.1038/s41421-022-00439-6. PMID:36085283 doi:http://dx.doi.org/10.1038/s41421-022-00439-6

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