2QYF

Crystal structure of the Mad2/p31(comet)/Mad2-binding peptide ternary complex

Summary for 2QYF

• Entry DOI: 10.2210/pdb2qyf/pdb
• Related: 1DUJ 1KLQ 1S2H
• Descriptor: Mitotic spindle assembly checkpoint protein MAD2A, MAD2L1-binding protein, peptide, ... (4 entities in total)
• Functional Keywords: protein-peptide complex, mad2 family, spindle assembly checkpoint, cell cycle, cell division, mitosis, nucleus, phosphorylation
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q13257 Q15013
• Total number of polymer chains: 6
• Total formula weight: 105470.54

Authors

Tomchick, D.R.,Luo, X. (deposition date: 2007-08-14, release date: 2008-01-29, Last modification date: 2024-10-30)

Primary citation

Yang, M.,Li, B.,Tomchick, D.R.,Machius, M.,Rizo, J.,Yu, H.,Luo, X.
p31comet blocks Mad2 activation through structural mimicry.
Cell(Cambridge,Mass.), 131:744-755, 2007

PubMed Abstract: The status of spindle checkpoint signaling depends on the balance of two opposing dynamic processes that regulate the highly unusual two-state behavior of Mad2. In mitosis, a Mad1-Mad2 core complex recruits cytosolic Mad2 to kinetochores through Mad2 dimerization and converts Mad2 to a conformer amenable to Cdc20 binding, thereby facilitating checkpoint activation. p31(comet) inactivates the checkpoint through binding to Mad1- or Cdc20-bound Mad2, thereby preventing Mad2 activation and promoting the dissociation of the Mad2-Cdc20 complex. Here, we report the crystal structure of the Mad2-p31(comet) complex. The C-terminal region of Mad2 that undergoes rearrangement in different Mad2 conformers is a major structural determinant for p31(comet) binding, explaining the specificity of p31(comet) toward Mad1- or Cdc20-bound Mad2. p31(comet) adopts a fold strikingly similar to that of Mad2 and binds at the dimerization interface of Mad2. Thus, p31(comet) exploits the two-state behavior of Mad2 to block its activation by acting as an "anti-Mad2."

PubMed: 18022368
DOI: 10.1016/j.cell.2007.08.048

Experimental method

X-RAY DIFFRACTION (2.3 Å)