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 language | English |
|---|---|
| Pages (from-to) | 730-743 |
| Number of pages | 14 |
| Journal | Cell |
| Volume | 131 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Nov 16 2007 |
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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 journal › Article
}
TY - JOUR
T1 - The Mad2 Conformational Dimer
T2 - Structure and Implications for the Spindle Assembly Checkpoint
AU - Mapelli, Marina
AU - Massimiliano, Lucia
AU - Santaguida, Stefano
AU - Musacchio, Andrea
PY - 2007/11/16
Y1 - 2007/11/16
N2 - 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.
AB - 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.
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=36049044125&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36049044125&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2007.08.049
DO - 10.1016/j.cell.2007.08.049
M3 - Article
C2 - 18022367
AN - SCOPUS:36049044125
VL - 131
SP - 730
EP - 743
JO - Cell
JF - Cell
SN - 0092-8674
IS - 4
ER -