Conformational mechanism for the stability of microtubule-kinetochore attachments

Biophys J. 2014 Jul 15;107(2):289-300. doi: 10.1016/j.bpj.2014.06.004.

Abstract

Regulating the stability of microtubule (MT)-kinetochore attachments is fundamental to avoiding mitotic errors and ensuring proper chromosome segregation during cell division. Although biochemical factors involved in this process have been identified, their mechanics still need to be better understood. Here we introduce and simulate a mechanical model of MT-kinetochore interactions in which the stability of the attachment is ruled by the geometrical conformations of curling MT-protofilaments entangled in kinetochore fibrils. The model allows us to reproduce, with good accuracy, in vitro experimental measurements of the detachment times of yeast kinetochores from MTs under external pulling forces. Numerical simulations suggest that geometrical features of MT-protofilaments may play an important role in the switch between stable and unstable attachments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / metabolism
  • Amino Acid Sequence
  • Kinetochores / chemistry*
  • Kinetochores / metabolism
  • Microtubules / chemistry*
  • Microtubules / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Protein Stability
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Saccharomyces cerevisiae Proteins