The yeast Ctf3 complex with Cnn1-Wip1The yeast Ctf3 complex with Cnn1-Wip1

Structural highlights

6wuc is a 5 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:WIP1 (ATCC 18824), CNN1 (ATCC 18824)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CENPW_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly (PubMed:22561346).[1] [CENPH_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[2] [CENPK_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[3] [CENPI_YEAST] Component of the central kinetochore, which mediates the attachment of the centromere to the mitotic spindle by forming essential interactions between the microtubule-associated outer kinetochore proteins and the centromere-associated inner kinetochore proteins. Required for establishing bipolar spindle-microtubule attachments and proper chromosome segregation. Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly.[4] [CENPT_YEAST] Component of the kinetochore, a multiprotein complex that assembles on centromeric DNA and attaches chromosomes to spindle microtubules, mediating chromosome segregation and sister chromatid segregation during meiosis and mitosis. Component of the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly (PubMed:22561346). CNN1 is important for the recruitment of the outer kinetochore Ndc80 complex (PubMed:23334295).[5] [6]

Publication Abstract from PubMed

Chromosome segregation depends on a regulated connection between spindle microtubules and centromeric DNA. The kinetochore mediates this connection and ensures it persists during anaphase, when sister chromatids must transit into daughter cells uninterrupted. The Ctf19 complex (Ctf19c) forms the centromeric base of the kinetochore in budding yeast. Biochemical experiments show that Ctf19c members associate hierarchically when purified from cell extract [1], an observation that is mostly explained by the structure of the complex [2]. The Ctf3 complex (Ctf3c), which is not required for the assembly of most other Ctf19c factors, disobeys the biochemical assembly hierarchy when observed in dividing cells that lack more basal components [3]. Thus, the biochemical experiments do not completely recapitulate the logic of centromeric Ctf19c assembly. We now present a high-resolution structure of the Ctf3c bound to the Cnn1-Wip1 heterodimer. Associated live-cell imaging experiments provide a mechanism for Ctf3c and Cnn1-Wip1 recruitment to the kinetochore. The mechanism suggests feedback regulation of Ctf19c assembly and unanticipated similarities in kinetochore organization between yeast and vertebrates.

The Structural Basis for Kinetochore Stabilization by Cnn1/CENP-T.,Hinshaw SM, Harrison SC Curr Biol. 2020 Sep 7;30(17):3425-3431.e3. doi: 10.1016/j.cub.2020.06.024. Epub, 2020 Jul 16. PMID:32679099[7]

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

References

  1. Schleiffer A, Maier M, Litos G, Lampert F, Hornung P, Mechtler K, Westermann S. CENP-T proteins are conserved centromere receptors of the Ndc80 complex. Nat Cell Biol. 2012 May 6;14(6):604-13. doi: 10.1038/ncb2493. PMID:22561346 doi:http://dx.doi.org/10.1038/ncb2493
  2. Sanyal K, Ghosh SK, Sinha P. The MCM16 gene of the yeast Saccharomyces cerevisiae is required for chromosome segregation. Mol Gen Genet. 1998 Nov;260(2-3):242-50. PMID:9862478
  3. Poddar A, Roy N, Sinha P. MCM21 and MCM22, two novel genes of the yeast Saccharomyces cerevisiae are required for chromosome transmission. Mol Microbiol. 1999 Jan;31(1):349-60. PMID:9987135
  4. Cheeseman IM, Anderson S, Jwa M, Green EM, Kang J, Yates JR 3rd, Chan CS, Drubin DG, Barnes G. Phospho-regulation of kinetochore-microtubule attachments by the Aurora kinase Ipl1p. Cell. 2002 Oct 18;111(2):163-72. PMID:12408861
  5. Schleiffer A, Maier M, Litos G, Lampert F, Hornung P, Mechtler K, Westermann S. CENP-T proteins are conserved centromere receptors of the Ndc80 complex. Nat Cell Biol. 2012 May 6;14(6):604-13. doi: 10.1038/ncb2493. PMID:22561346 doi:http://dx.doi.org/10.1038/ncb2493
  6. Malvezzi F, Litos G, Schleiffer A, Heuck A, Mechtler K, Clausen T, Westermann S. A structural basis for kinetochore recruitment of the Ndc80 complex via two distinct centromere receptors. EMBO J. 2013 Feb 6;32(3):409-23. doi: 10.1038/emboj.2012.356. Epub 2013 Jan 18. PMID:23334295 doi:http://dx.doi.org/10.1038/emboj.2012.356
  7. Hinshaw SM, Harrison SC. The Structural Basis for Kinetochore Stabilization by Cnn1/CENP-T. Curr Biol. 2020 Sep 7;30(17):3425-3431.e3. doi: 10.1016/j.cub.2020.06.024. Epub, 2020 Jul 16. PMID:32679099 doi:http://dx.doi.org/10.1016/j.cub.2020.06.024

6wuc, resolution 3.23Å

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