Kinesin-5 promotes microtubule nucleation and assembly by stabilizing a lattice-competent conformation of tubulin

Geng Yuan Chen, Ana B. Asenjo, Yalei Chen, Jake Mascaro, D. F.J. Arginteanu, Hernando J. Sosa, William O. Hancock

Research output: Contribution to journalArticlepeer-review

Abstract

Besides sliding apart antiparallel microtubules during spindle elongation, the mitotic kinesin-5, Eg5 promotes microtubule polymerization, emphasizing its importance in mitotic spindle length control. Here, we characterize the Eg5 microtubule polymerase mechanism by assessing motor-induced changes in the longitudinal and lateral tubulin-tubulin bonds that form the microtubule lattice. Isolated Eg5 motor domains promote microtubule nucleation, growth and stability. Eg5 binds preferentially to microtubules over free tubulin, and colchicine-like inhibitors that stabilize the bent conformation of tubulin allosterically inhibit Eg5 binding, consistent with a model in which Eg5 induces a curved-to-straight transition in tubulin. Domain swap experiments establish that the family-specific Loop11, which resides near the nucleotide-sensing Switch-II domain, is necessary and sufficient for the polymerase activity of Eg5. Thus, we propose a microtubule polymerase mechanism in which Eg5 at the plus-end promotes a curved-to-straight transition in tubulin that enhances lateral bond formation and thereby promotes microtubule growth and stability.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Jan 14 2019

Keywords

  • coupled-equilibria
  • Eg5
  • Kinesin
  • microtubule
  • microtubule dynamics
  • microtubule-associated proteins
  • tubulin wedge inhibitors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'Kinesin-5 promotes microtubule nucleation and assembly by stabilizing a lattice-competent conformation of tubulin'. Together they form a unique fingerprint.

Cite this