The Mad2 Conformational Dimer: Structure and Implications for the Spindle Assembly Checkpoint

Marina Mapelli, Lucia Massimiliano, Stefano Santaguida, Andrea Musacchio

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

The 25 kDa Mad2 protein is a key player in the spindle assembly checkpoint, a safeguard against chromosome segregation errors in mitosis. Mad2 combines three unusual properties. First, Mad2 adopts two conformations with distinct topologies, open (O) and closed (C) Mad2. Second, C-Mad2 forms topological links with its two best-characterized protein ligands, Mad1 and Cdc20. Third, O-Mad2 and C-Mad2 engage in a "conformational" dimer that is essential for spindle checkpoint function in different organisms. The crystal structure of the O-Mad2-C-Mad2 conformational dimer, reported here, reveals an asymmetric interface that explains the selective dimerization of the O-Mad2 and C-Mad2 conformers. The structure also identifies several buried hydrophobic residues whose rearrangement correlates with the Mad2 topological change. The structure of the O-Mad2-C-Mad2 conformational dimer is consistent with a catalytic model in which a C-Mad2 template facilitates the binding of O-Mad2 to Cdc20, the target of Mad2 in the spindle checkpoint.

Original languageEnglish
Pages (from-to)730-743
Number of pages14
JournalCell
Volume131
Issue number4
DOIs
Publication statusPublished - Nov 16 2007

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Mad2 Proteins
M Phase Cell Cycle Checkpoints
Chromosome Segregation
Dimerization
Mitosis
Dimers
Ligands
Proteins
Chromosomes
Conformations
Crystal structure
Topology

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

The Mad2 Conformational Dimer : Structure and Implications for the Spindle Assembly Checkpoint. / Mapelli, Marina; Massimiliano, Lucia; Santaguida, Stefano; Musacchio, Andrea.

In: Cell, Vol. 131, No. 4, 16.11.2007, p. 730-743.

Research output: Contribution to journalArticle

Mapelli, Marina ; Massimiliano, Lucia ; Santaguida, Stefano ; Musacchio, Andrea. / The Mad2 Conformational Dimer : Structure and Implications for the Spindle Assembly Checkpoint. In: Cell. 2007 ; Vol. 131, No. 4. pp. 730-743.
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