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KIF14 binds tightly to microtubules and adopts a rigor-like conformation.

Arora K, Talje L, Asenjo AB, Andersen P, Atchia K, Joshi M, Sosa H, Allingham JS, Kwok BH
J Mol Biol 426 2997-3015 (2014)
Cited: 32 times
EuropePMC logo PMID: 24949858

Abstract

The mitotic kinesin motor protein KIF14 is essential for cytokinesis during cell division and has been implicated in cerebral development and a variety of human cancers. Here we show that the mouse KIF14 motor domain binds tightly to microtubules and does not display typical nucleotide-dependent changes in this affinity. It also has robust ATPase activity but very slow motility. A crystal structure of the ADP-bound form of the KIF14 motor domain reveals a dramatically opened ATP-binding pocket, as if ready to exchange its bound ADP for Mg·ATP. In this state, the central β-sheet is twisted ~10° beyond the maximal amount observed in other kinesins. This configuration has only been seen in the nucleotide-free states of myosins-known as the "rigor-like" state. Fitting of this atomic model to electron density maps from cryo-electron microscopy indicates a distinct binding configuration of the motor domain to microtubules. We postulate that these properties of KIF14 are well suited for stabilizing midbody microtubules during cytokinesis.

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Reviews citing this publication (7)

  1. Dissecting the Genetic and Etiological Causes of Primary Microcephaly. Jean F, Stuart A, Tarailo-Graovac M. Front Neurol 11 570830 (2020)
  2. Kinesin, 30 years later: Recent insights from structural studies. Wang W, Cao L, Wang C, Gigant B, Knossow M. Protein Sci 24 1047-1056 (2015)
  3. Molecular Genetics of Microcephaly Primary Hereditary: An Overview. Siskos N, Stylianopoulou E, Skavdis G, Grigoriou ME. Brain Sci 11 581 (2021)
  4. Inhibiting microcephaly genes as alternative to microtubule targeting agents to treat brain tumors. Iegiani G, Di Cunto F, Pallavicini G. Cell Death Dis 12 956 (2021)
  5. Emerging role of microtubule-associated proteins on cancer metastasis. Wattanathamsan O, Pongrakhananon V. Front Pharmacol 13 935493 (2022)
  6. Cytoskeletal and Cytoskeleton-Associated Proteins: Key Regulators of Cancer Stem Cell Properties. Li Y, Wang D, Ge H, Güngör C, Gong X, Chen Y. Pharmaceuticals (Basel) 15 1369 (2022)
  7. New insights into the mechanochemical coupling mechanism of kinesin-microtubule complexes from their high-resolution structures. Benoit MPMH, Hunter B, Allingham JS, Sosa H. Biochem Soc Trans 51 1505-1520 (2023)

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