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2qyf
From Proteopedia
| 2qyf, resolution 2.30Å () | |||||||||
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| Non-Standard Residues: | |||||||||
| Gene: | MAD2L1, MAD2 (Homo sapiens), MAD2L1BP, CMT2, KIAA0110 (Homo sapiens) | ||||||||
| Related: | 1s2h, 1klq, 1duj | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Crystal structure of the Mad2/p31(comet)/Mad2-binding peptide ternary complex
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."
p31comet blocks Mad2 activation through structural mimicry., Yang M, Li B, Tomchick DR, Machius M, Rizo J, Yu H, Luo X, Cell. 2007 Nov 16;131(4):744-55. PMID:18022368
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2qyf is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Yang M, Li B, Tomchick DR, Machius M, Rizo J, Yu H, Luo X. p31comet blocks Mad2 activation through structural mimicry. Cell. 2007 Nov 16;131(4):744-55. PMID:18022368 doi:10.1016/j.cell.2007.08.048
- Luo X, Tang Z, Xia G, Wassmann K, Matsumoto T, Rizo J, Yu H. The Mad2 spindle checkpoint protein has two distinct natively folded states. Nat Struct Mol Biol. 2004 Apr;11(4):338-45. Epub 2004 Mar 14. PMID:15024386 doi:10.1038/nsmb748
- Luo X, Tang Z, Rizo J, Yu H. The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20. Mol Cell. 2002 Jan;9(1):59-71. PMID:11804586
- Luo X, Fang G, Coldiron M, Lin Y, Yu H, Kirschner MW, Wagner G. Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20. Nat Struct Biol. 2000 Mar;7(3):224-9. PMID:10700282 doi:10.1038/73338
