Insight into microtubule nucleation from tubulin-capping proteins

Proc Natl Acad Sci U S A. 2019 May 14;116(20):9859-9864. doi: 10.1073/pnas.1813559116. Epub 2019 Apr 29.


Nucleation is one of the least understood steps of microtubule dynamics. It is a kinetically unfavorable process that is templated in the cell by the γ-tubulin ring complex or by preexisting microtubules; it also occurs in vitro from pure tubulin. Here we study the nucleation inhibition potency of natural or artificial proteins in connection with their binding mode to the longitudinal surface of α- or β-tubulin. The structure of tubulin-bound CopN, a Chlamydia protein that delays nucleation, suggests that this protein may interfere with two protofilaments at the (+) end of a nucleus. Designed ankyrin repeat proteins that share a binding mode similar to that of CopN also impede nucleation, whereas those that target only one protofilament do not. In addition, an αRep protein predicted to target two protofilaments at the (-) end does not delay nucleation, pointing to different behaviors at both ends of the nucleus. Our results link the interference with protofilaments at the (+) end and the inhibition of nucleation.

Keywords: CopN; artificial binding proteins; cytoskeleton; microtubule nucleation; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism*
  • Chlamydophila pneumoniae
  • Microtubules / metabolism*
  • Tubulin / metabolism*


  • Bacterial Proteins
  • Tubulin

Associated data

  • PDB/6GX7
  • PDB/6GVM
  • PDB/6GVN