2V64

Crystallographic structure of the conformational dimer of the Spindle Assembly Checkpoint protein Mad2.

Summary for 2V64

• Entry DOI: 10.2210/pdb2v64/pdb
• Related: 1DUJ 1GO4 1KLQ 1S2H
• Descriptor: MITOTIC SPINDLE ASSEMBLY CHECKPOINT PROTEIN MAD2A, MBP1, ... (4 entities in total)
• Functional Keywords: spindle assembly checkpoint, mad2, nucleus, mitosis, apoptosis, cell cycle, cell division, phosphorylation, conformational dimer
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: Q13257 Q13257
• Total number of polymer chains: 9
• Total formula weight: 149167.73

Authors

Mapelli, M.,Massimiliano, L.,Santaguida, S.,Musacchio, A. (deposition date: 2007-07-13, release date: 2007-11-27, Last modification date: 2024-10-23)

Primary citation

Mapelli, M.,Massimiliano, L.,Santaguida, S.,Musacchio, A.
The MAD2 Conformational Dimer: Structure and Implications for the Spindle Assembly Checkpoint
Cell(Cambridge,Mass.), 131:730-, 2007

PubMed 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.

PubMed: 18022367
DOI: 10.1016/J.CELL.2007.08.049

Experimental method

X-RAY DIFFRACTION (2.9 Å)