8q5h

Human KMN network (outer kinetochore)Human KMN network (outer kinetochore)

Structural highlights

8q5h is a 7 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 4.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPC24_HUMAN Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:14738735). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:14738735). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020).^[1] ^[2]

Publication Abstract from PubMed

Biorientation of chromosomes during cell division is necessary for precise dispatching of a mother cell's chromosomes into its two daughters. Kinetochores, large layered structures built on specialized chromosome loci named centromeres, promote biorientation by binding and sensing spindle microtubules. One of the outer layer main components is a ten-subunit assembly comprising Knl1C, Mis12C and Ndc80C (KMN) subcomplexes. The KMN is highly elongated and docks on kinetochores and microtubules through interfaces at its opposite extremes. Here, we combine cryogenic electron microscopy reconstructions and AlphaFold2 predictions to generate a model of the human KMN that reveals all intra-KMN interfaces. We identify and functionally validate two interaction interfaces that link Mis12C to Ndc80C and Knl1C. Through targeted interference experiments, we demonstrate that this mutual organization strongly stabilizes the KMN assembly. Our work thus reports a comprehensive structural and functional analysis of this part of the kinetochore microtubule-binding machinery and elucidates the path of connections from the chromatin-bound components to the force-generating components.

Structure of the human KMN complex and implications for regulation of its assembly.,Polley S, Raisch T, Ghetti S, Korner M, Terbeck M, Grater F, Raunser S, Aponte-Santamaria C, Vetter IR, Musacchio A Nat Struct Mol Biol. 2024 Jun;31(6):861-873. doi: 10.1038/s41594-024-01230-9. , Epub 2024 Mar 8. PMID:38459128^[3]

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

References

↑ McCleland ML, Kallio MJ, Barrett-Wilt GA, Kestner CA, Shabanowitz J, Hunt DF, Gorbsky GJ, Stukenberg PT. The vertebrate Ndc80 complex contains Spc24 and Spc25 homologs, which are required to establish and maintain kinetochore-microtubule attachment. Curr Biol. 2004 Jan 20;14(2):131-7. PMID:14738735 doi:10.1016/j.cub.2003.12.058
↑ Schmidt JC, Arthanari H, Boeszoermenyi A, Dashkevich NM, Wilson-Kubalek EM, Monnier N, Markus M, Oberer M, Milligan RA, Bathe M, Wagner G, Grishchuk EL, Cheeseman IM. The Kinetochore-Bound Ska1 Complex Tracks Depolymerizing Microtubules and Binds to Curved Protofilaments. Dev Cell. 2012 Oct 17. pii: S1534-5807(12)00423-6. doi:, 10.1016/j.devcel.2012.09.012. PMID:23085020 doi:http://dx.doi.org/10.1016/j.devcel.2012.09.012
↑ Polley S, Raisch T, Ghetti S, Körner M, Terbeck M, Gräter F, Raunser S, Aponte-Santamaría C, Vetter IR, Musacchio A. Structure of the human KMN complex and implications for regulation of its assembly. Nat Struct Mol Biol. 2024 Jun;31(6):861-873. PMID:38459128 doi:10.1038/s41594-024-01230-9

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OCA

[1] McCleland ML, Kallio MJ, Barrett-Wilt GA, Kestner CA, Shabanowitz J, Hunt DF, Gorbsky GJ, Stukenberg PT. The vertebrate Ndc80 complex contains Spc24 and Spc25 homologs, which are required to establish and maintain kinetochore-microtubule attachment. Curr Biol. 2004 Jan 20;14(2):131-7. PMID:14738735 doi:10.1016/j.cub.2003.12.058

[2] Schmidt JC, Arthanari H, Boeszoermenyi A, Dashkevich NM, Wilson-Kubalek EM, Monnier N, Markus M, Oberer M, Milligan RA, Bathe M, Wagner G, Grishchuk EL, Cheeseman IM. The Kinetochore-Bound Ska1 Complex Tracks Depolymerizing Microtubules and Binds to Curved Protofilaments. Dev Cell. 2012 Oct 17. pii: S1534-5807(12)00423-6. doi:, 10.1016/j.devcel.2012.09.012. PMID:23085020 doi:http://dx.doi.org/10.1016/j.devcel.2012.09.012

[3] Polley S, Raisch T, Ghetti S, Körner M, Terbeck M, Gräter F, Raunser S, Aponte-Santamaría C, Vetter IR, Musacchio A. Structure of the human KMN complex and implications for regulation of its assembly. Nat Struct Mol Biol. 2024 Jun;31(6):861-873. PMID:38459128 doi:10.1038/s41594-024-01230-9

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[2]

[3]

8q5h

Human KMN network (outer kinetochore)Human KMN network (outer kinetochore)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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8q5h

Human KMN network (outer kinetochore)Human KMN network (outer kinetochore)

Structural highlights

Function

Publication Abstract from PubMed

References

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