Explaining the oligomerization properties of the spindle assembly checkpoint protein Mad2

Anna DeAntoni, Valeria Sala, Andrea Musacchio, M. Herbert, J. K. Heriche, T. Mitchison

Research output: Contribution to journalArticle

Abstract

Mad2 is an essential component of the spindle assembly checkpoint (SAC), a molecular device designed to coordinate anaphase onset with the completion of chromosome attachment to the spindle. Capture of chromosome by microtubules occur on protein scaffolds known as kinetochores. The SAC proteins are recruited to kinetochores in prometaphase where they generate a signal that halts anaphase until all sister chromatid pairs are bipolarly oriented. Mad2 is a subunit of the mitotic checkpoint complex, which is regarded as the effector of the spindle checkpoint. Its function is the sequestration of Cdc20, a protein required for progression into anaphase. The function of Mad2 in the checkpoint correlates with a dramatic conformational rearrangement of the Mad2 protein. Mad2 adopts a closed conformation (C-Mad2) when bound to Cdc20, and an open conformation (O-Mad2) when unbound to this ligand. Checkpoint activation promotes the conversion of O-Mad2 to Cdc20-bound C-Mad2. We show that this conversion requires a C-Mad2 template and we identify this in Mad1-bound Mad2. In our proposition, Mad1-bound C-Mad2 recruits O-Mad2 to kinetochores, stimulating Cdc20 capture, implying that O-Mad2 and C-Mad2 form dimers. We discuss Mad2 oligomerization and link our discoveries to previous observations related to Mad2 oligomerization.

Original languageEnglish
Pages (from-to)637-648
Number of pages12
JournalPhilosophical transactions of the Royal Society of London. Series B: Biological sciences
Volume360
Issue number1455
DOIs
Publication statusPublished - Mar 29 2005

Fingerprint

Mad2 Proteins
M Phase Cell Cycle Checkpoints
Kinetochores
kinetochores
Oligomerization
Anaphase
anaphase
Chromosomes
Cdc20 Proteins
protein
Conformations
scaffolding proteins
Prometaphase
chromosomes
chromosome
Proteins
Chromatids
chromatids
proteins
Scaffolds

Keywords

  • Cdc20
  • Kinetochore
  • Mad1
  • Mad2
  • Metaphase
  • Spindle checkpoint

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Agricultural and Biological Sciences (miscellaneous)

Cite this

Explaining the oligomerization properties of the spindle assembly checkpoint protein Mad2. / DeAntoni, Anna; Sala, Valeria; Musacchio, Andrea; Herbert, M.; Heriche, J. K.; Mitchison, T.

In: Philosophical transactions of the Royal Society of London. Series B: Biological sciences, Vol. 360, No. 1455, 29.03.2005, p. 637-648.

Research output: Contribution to journalArticle

DeAntoni, Anna ; Sala, Valeria ; Musacchio, Andrea ; Herbert, M. ; Heriche, J. K. ; Mitchison, T. / Explaining the oligomerization properties of the spindle assembly checkpoint protein Mad2. In: Philosophical transactions of the Royal Society of London. Series B: Biological sciences. 2005 ; Vol. 360, No. 1455. pp. 637-648.
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