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Structure paper

TitleHURP regulates Kif18A recruitment and activity to synergistically control microtubule dynamics.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 9687, Year 2024
Publish dateNov 8, 2024
AuthorsJuan M Perez-Bertoldi / Yuanchang Zhao / Akanksha Thawani / Ahmet Yildiz / Eva Nogales /
PubMed AbstractDuring mitosis, microtubule dynamics are regulated to ensure proper alignment and segregation of chromosomes. The dynamics of kinetochore-attached microtubules are regulated by hepatoma-upregulated ...During mitosis, microtubule dynamics are regulated to ensure proper alignment and segregation of chromosomes. The dynamics of kinetochore-attached microtubules are regulated by hepatoma-upregulated protein (HURP) and the mitotic kinesin-8 Kif18A, but the underlying mechanism remains elusive. Using single-molecule imaging in vitro, we demonstrate that Kif18A motility is regulated by HURP. While sparse decoration of HURP activates the motor, higher concentrations hinder processive motility. To shed light on this behavior, we determine the binding mode of HURP to microtubules using cryo-EM. The structure helps rationalize why HURP functions as a microtubule stabilizer. Additionally, HURP partially overlaps with the microtubule-binding site of the Kif18A motor domain, indicating that excess HURP inhibits Kif18A motility by steric exclusion. We also observe that HURP and Kif18A function together to suppress dynamics of the microtubule plus-end, providing a mechanistic basis for how they collectively serve in microtubule length control.
External linksNat Commun / PubMed:39516196 / PubMed Central
MethodsEM (helical sym.)
Resolution3.1 - 3.3 Å
Structure data

46893

9dhz

9dxc

EMDB-46893, PDB-9dhz:
Cryo-EM structure of HURP bound to a microtubule
PDB-9dxc: Model of tubulin dimers used for determining the dimer rise in a taxol-stabilized microtubule-HURP complex
Method: EM (helical sym.) / Resolution: 3.1 Å

46894

9di0

EMDB-46894, PDB-9di0:
Cryo-EM structure of Kif18A bound to a microtubule
Method: EM (helical sym.) / Resolution: 3.1 Å

47285

9dxe

EMDB-47285, PDB-9dxe:
Model of tubulin dimers used for determining the dimer rise in a taxol-stabilized microtubule
Method: EM (helical sym.) / Resolution: 3.3 Å

Chemicals

ChemComp-TA1:
TAXOL / medication, chemotherapy*YM

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Source
  • homo sapiens (human)
  • sus scrofa (pig)
KeywordsPROTEIN BINDING / HURP / Tubulin / K-fiber / mitosis / spindle / Kif18A / STRUCTURAL PROTEIN

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