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TitleModular assembly of RWD domains on the Mis12 complex underlies outer kinetochore organization.
Journal, issue, pagesMol Cell, Vol. 53, Issue 4, Page 591-605, Year 2014
Publish dateFeb 20, 2014
AuthorsArsen Petrovic / Shyamal Mosalaganti / Jenny Keller / Marta Mattiuzzo / Katharina Overlack / Veronica Krenn / Anna De Antoni / Sabine Wohlgemuth / Valentina Cecatiello / Sebastiano Pasqualato / Stefan Raunser / Andrea Musacchio /
PubMed AbstractFaithful chromosome segregation is mandatory for cell and organismal viability. Kinetochores, large protein assemblies embedded in centromeric chromatin, establish a mechanical link between ...Faithful chromosome segregation is mandatory for cell and organismal viability. Kinetochores, large protein assemblies embedded in centromeric chromatin, establish a mechanical link between chromosomes and spindle microtubules. The KMN network, a conserved 10-subunit kinetochore complex, harbors the microtubule-binding interface. RWD domains in the KMN subunits Spc24 and Spc25 mediate kinetochore targeting of the microtubule-binding subunits by interacting with the Mis12 complex, a KMN subcomplex that tethers directly onto the underlying chromatin layer. Here, we show that Knl1, a KMN subunit involved in mitotic checkpoint signaling, also contains RWD domains that bind the Mis12 complex and that mediate kinetochore targeting of Knl1. By reporting the first 3D electron microscopy structure of the KMN network, we provide a comprehensive framework to interpret how interactions of RWD-containing proteins with the Mis12 complex shape KMN network topology. Our observations unveil a regular pattern in the construction of the outer kinetochore.
External linksMol Cell / PubMed:24530301
MethodsEM (single particle) / X-ray diffraction
Resolution2.497 - 26.7 Å
Structure data

EMDB-2549:
3D structure of the KMN network
Method: EM (single particle) / Resolution: 26.7 Å

PDB-4nf9:
Structure of the Knl1/Nsl1 complex
Method: X-RAY DIFFRACTION / Resolution: 2.8 Å

PDB-4nfa:
Structure of the C-terminal doamin of Knl1
Method: X-RAY DIFFRACTION / Resolution: 2.497 Å

Chemicals

ChemComp-CL:
Unknown entry / Chloride

ChemComp-HOH:
WATER / Water

ChemComp-GOL:
GLYCEROL / Glycerol

Source
  • homo sapiens (human)
KeywordsCELL CYCLE / RWD domain

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