5mu3 | pdb_00005mu3
Crystal structure of Ctf19-Mcm21 kinetochore assembly bound with Ctf19-Mcm21 binding motif of central kinetochore subunit Okp1
Structural highlights
FunctionCENPO_KLULA 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 (By similarity). Component of the inner kinetochore COMA subcomplex, which connects centromere-associated proteins and the outer kinetochore (PubMed:29046335). COMA interacts with other inner kinetochore proteins to form the inner kinetochore constitutive centromere-associated network (CCAN), which serves as a structural platform for outer kinetochore assembly (By similarity).[UniProtKB:Q06675][1] Publication Abstract from PubMedKinetochores are dynamic cellular structures that connect chromosomes to microtubules. They form from multi-protein assemblies that are evolutionarily conserved between yeasts and humans. One of these assemblies-COMA-consists of subunits Ame1CENP-U, Ctf19CENP-P, Mcm21CENP-O and Okp1CENP-Q A description of COMA molecular organization has so far been missing. We defined the subunit topology of COMA, bound with inner kinetochore proteins Nkp1 and Nkp2, from the yeast Kluyveromyces lactis, with nanoflow electrospray ionization mass spectrometry, and mapped intermolecular contacts with hydrogen-deuterium exchange coupled to mass spectrometry. Our data suggest that the essential Okp1 subunit is a multi-segmented nexus with distinct binding sites for Ame1, Nkp1-Nkp2 and Ctf19-Mcm21. Our crystal structure of the Ctf19-Mcm21 RWD domains bound with Okp1 shows the molecular contacts of this important inner kinetochore joint. The Ctf19-Mcm21 binding motif in Okp1 configures a branch of mitotic inner kinetochores, by tethering Ctf19-Mcm21 and Chl4CENP-N-Iml3CENP-L Absence of this motif results in dependence on the mitotic checkpoint for viability. Molecular basis for inner kinetochore configuration through RWD domain-peptide interactions.,Schmitzberger F, Richter MM, Gordiyenko Y, Robinson CV, Dadlez M, Westermann S EMBO J. 2017 Oct 18. pii: e201796636. doi: 10.15252/embj.201796636. PMID:29046335[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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