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| | ==Crystal structure of the Mad2/p31(comet)/Mad2-binding peptide ternary complex== | | ==Crystal structure of the Mad2/p31(comet)/Mad2-binding peptide ternary complex== |
| - | <StructureSection load='2qyf' size='340' side='right' caption='[[2qyf]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='2qyf' size='340' side='right'caption='[[2qyf]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qyf]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QYF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QYF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qyf]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QYF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QYF FirstGlance]. <br> |
| | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1s2h|1s2h]], [[1klq|1klq]], [[1duj|1duj]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1s2h|1s2h]], [[1klq|1klq]], [[1duj|1duj]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAD2L1, MAD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MAD2L1BP, CMT2, KIAA0110 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAD2L1, MAD2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MAD2L1BP, CMT2, KIAA0110 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qyf OCA], [http://pdbe.org/2qyf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qyf RCSB], [http://www.ebi.ac.uk/pdbsum/2qyf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qyf ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qyf OCA], [https://pdbe.org/2qyf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qyf RCSB], [https://www.ebi.ac.uk/pdbsum/2qyf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qyf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MD2L1_HUMAN MD2L1_HUMAN]] Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Required for the execution of the mitotic checkpoint which monitors the process of kinetochore-spindle attachment and inhibits the activity of the anaphase promoting complex by sequestering CDC20 until all chromosomes are aligned at the metaphase plate.<ref>PMID:10700282</ref> <ref>PMID:11804586</ref> <ref>PMID:15024386</ref> [[http://www.uniprot.org/uniprot/MD2BP_HUMAN MD2BP_HUMAN]] May function to silence the spindle checkpoint and allow mitosis to proceed through anaphase by binding MAD2L1 after it has become dissociated from the MAD2L1-CDC20 complex.<ref>PMID:12456649</ref> <ref>PMID:18022368</ref> | + | [[https://www.uniprot.org/uniprot/MD2L1_HUMAN MD2L1_HUMAN]] Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Required for the execution of the mitotic checkpoint which monitors the process of kinetochore-spindle attachment and inhibits the activity of the anaphase promoting complex by sequestering CDC20 until all chromosomes are aligned at the metaphase plate.<ref>PMID:10700282</ref> <ref>PMID:11804586</ref> <ref>PMID:15024386</ref> [[https://www.uniprot.org/uniprot/MD2BP_HUMAN MD2BP_HUMAN]] May function to silence the spindle checkpoint and allow mitosis to proceed through anaphase by binding MAD2L1 after it has become dissociated from the MAD2L1-CDC20 complex.<ref>PMID:12456649</ref> <ref>PMID:18022368</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Luo, X]] | | [[Category: Luo, X]] |
| | [[Category: Tomchick, D R]] | | [[Category: Tomchick, D R]] |
| Structural highlights
Function
[MD2L1_HUMAN] Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Required for the execution of the mitotic checkpoint which monitors the process of kinetochore-spindle attachment and inhibits the activity of the anaphase promoting complex by sequestering CDC20 until all chromosomes are aligned at the metaphase plate.[1] [2] [3] [MD2BP_HUMAN] May function to silence the spindle checkpoint and allow mitosis to proceed through anaphase by binding MAD2L1 after it has become dissociated from the MAD2L1-CDC20 complex.[4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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, 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
- ↑ Habu T, Kim SH, Weinstein J, Matsumoto T. Identification of a MAD2-binding protein, CMT2, and its role in mitosis. EMBO J. 2002 Dec 2;21(23):6419-28. PMID:12456649
- ↑ 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
- ↑ 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
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