Architecture of the Dam1 kinetochore ring complex and implications for microtubule-driven assembly and force-coupling mechanisms

Nat Struct Mol Biol. 2007 Aug;14(8):721-6. doi: 10.1038/nsmb1274. Epub 2007 Jul 22.

Abstract

The Dam1 kinetochore complex is essential for chromosome segregation in budding yeast. This ten-protein complex self-assembles around microtubules, forming ring-like structures that move with depolymerizing microtubule ends, a mechanism with implications for cellular function. Here we used EM-based single-particle and helical analyses to define the architecture of the Dam1 complex at 30-A resolution and the self-assembly mechanism. Ring oligomerization seems to be facilitated by a conformational change upon binding to microtubules, suggesting that the Dam1 ring is not preformed, but self-assembles around kinetochore microtubules. The C terminus of the Dam1p protein, where most of the Aurora kinase Ipl1 phosphorylation sites reside, is in a strategic location to affect oligomerization and interactions with the microtubule. One of Ipl1's roles might be to fine-tune the coupling of the microtubule interaction with the conformational change required for oligomerization, with phosphorylation resulting in ring breakdown.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / ultrastructure
  • Kinetochores / chemistry*
  • Kinetochores / ultrastructure
  • Microtubule-Associated Proteins / chemistry*
  • Microtubule-Associated Proteins / ultrastructure
  • Microtubules / chemistry
  • Microtubules / physiology*
  • Models, Molecular
  • Molecular Structure
  • Phosphorylation
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / ultrastructure

Substances

  • Cell Cycle Proteins
  • DAM1 protein, S cerevisiae
  • Microtubule-Associated Proteins
  • Saccharomyces cerevisiae Proteins