The Chlamydia effector chlamydial outer protein N (CopN) sequesters tubulin and prevents microtubule assembly

J Biol Chem. 2011 Sep 30;286(39):33992-8. doi: 10.1074/jbc.M111.258426. Epub 2011 Aug 13.


Chlamydia species are obligate intracellular pathogens that utilize a type three secretion system to manipulate host cell processes. Genetic manipulations are currently not possible in Chlamydia, necessitating study of effector proteins in heterologous expression systems and severely complicating efforts to relate molecular strategies used by Chlamydia to the biochemical activities of effector proteins. CopN is a chlamydial type three secretion effector that is essential for virulence. Heterologous expression of CopN in cells results in loss of microtubule spindles and metaphase plate formation and causes mitotic arrest. CopN is a multidomain protein with similarity to type three secretion system "plug" proteins from other organisms but has functionally diverged such that it also functions as an effector protein. We show that CopN binds directly to αβ-tubulin but not to microtubules (MTs). Furthermore, CopN inhibits tubulin polymerization by sequestering free αβ-tubulin, similar to one of the mechanisms utilized by stathmin. Although CopN and stathmin share no detectable sequence identity, both influence MT formation by sequestration of αβ-tubulin. CopN displaces stathmin from preformed stathmin-tubulin complexes, indicating that the proteins bind overlapping sites on tubulin. CopN is the first bacterial effector shown to disrupt MT formation directly. This recognition affords a mechanistic understanding of a strategy Chlamydia species use to manipulate the host cell cycle.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Cattle
  • Chlamydia / chemistry
  • Chlamydia / genetics
  • Chlamydia / metabolism*
  • Chlamydia / pathogenicity*
  • Chlamydia Infections / genetics
  • Chlamydia Infections / metabolism
  • Metaphase
  • Microtubules / chemistry
  • Microtubules / genetics
  • Microtubules / metabolism*
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism
  • Tubulin / chemistry
  • Tubulin / genetics
  • Tubulin / metabolism*
  • Virulence Factors / chemistry
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*


  • Bacterial Outer Membrane Proteins
  • Tubulin
  • Virulence Factors