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TitleStructural basis for Mis18 complex assembly and its implications for centromere maintenance.
Journal, issue, pagesEMBO Rep, Vol. 25, Issue 8, Page 3348-3372, Year 2024
Publish dateJul 1, 2024
AuthorsReshma Thamkachy / Bethan Medina-Pritchard / Sang Ho Park / Carla G Chiodi / Juan Zou / Maria de la Torre-Barranco / Kazuma Shimanaka / Maria Alba Abad / Cristina Gallego Páramo / Regina Feederle / Emilija Ruksenaite / Patrick Heun / Owen R Davies / Juri Rappsilber / Dina Schneidman-Duhovny / Uhn-Soo Cho / A Arockia Jeyaprakash /
PubMed AbstractThe centromere, defined by the enrichment of CENP-A (a Histone H3 variant) containing nucleosomes, is a specialised chromosomal locus that acts as a microtubule attachment site. To preserve ...The centromere, defined by the enrichment of CENP-A (a Histone H3 variant) containing nucleosomes, is a specialised chromosomal locus that acts as a microtubule attachment site. To preserve centromere identity, CENP-A levels must be maintained through active CENP-A loading during the cell cycle. A central player mediating this process is the Mis18 complex (Mis18α, Mis18β and Mis18BP1), which recruits the CENP-A-specific chaperone HJURP to centromeres for CENP-A deposition. Here, using a multi-pronged approach, we characterise the structure of the Mis18 complex and show that multiple hetero- and homo-oligomeric interfaces facilitate the hetero-octameric Mis18 complex assembly composed of 4 Mis18α, 2 Mis18β and 2 Mis18BP1. Evaluation of structure-guided/separation-of-function mutants reveals structural determinants essential for cell cycle controlled Mis18 complex assembly and centromere maintenance. Our results provide new mechanistic insights on centromere maintenance, highlighting that while Mis18α can associate with centromeres and deposit CENP-A independently of Mis18β, the latter is indispensable for the optimal level of CENP-A loading required for preserving the centromere identity.
External linksEMBO Rep / PubMed:38951710 / PubMed Central
MethodsEM (single particle)
Resolution24.8 - 27.8 Å
Structure data

EMDB-50218: Negative staining EM map for Mis18 core complex
Method: EM (single particle) / Resolution: 27.3 Å

EMDB-50219: Negative staining EM map for Mis18 core complex
Method: EM (single particle) / Resolution: 24.8 Å

EMDB-50220: Negative staining EM map for Mis18 core complex
Method: EM (single particle) / Resolution: 27.8 Å

Source
  • Homo sapiens (human)

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