1go4

From Proteopedia

(Difference between revisions)

Revision as of 05:58, 20 June 2018

Crystal structure of Mad1-Mad2 reveals a conserved Mad2 binding motif in Mad1 and Cdc20.

Structural highlights

1go4 is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1duj
Gene:	MAD2L1, MAD2 (HUMAN), MAD1L1, MAD1, TXBP181 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MD1L1_HUMAN] Defects in MAD1L1 are involved in the development and/or progression of various types of cancer.

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] [MD1L1_HUMAN] Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. May recruit MAD2L1 to unattached kinetochores. Has a role in the correct positioning of the septum. Required for anchoring MAD2L1 to the nuclear periphery. Binds to the TERT promoter and represses telomerase expression, possibly by interfering with MYC binding.^[4] ^[5] ^[6]

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 spindle checkpoint protein Mad1 recruits Mad2 to unattached kinetochores and is essential for Mad2-Cdc20 complex formation in vivo but not in vitro. The crystal structure of the Mad1-Mad2 complex reveals an asymmetric tetramer, with elongated Mad1 monomers parting from a coiled-coil to form two connected sub-complexes with Mad2. The Mad2 C-terminal tails are hinged mobile elements wrapping around the elongated ligands like molecular 'safety belts'. We show that Mad1 is a competitive inhibitor of the Mad2-Cdc20 complex, and propose that the Mad1-Mad2 complex acts as a regulated gate to control Mad2 release for Cdc20 binding. Mad1-Mad2 is strongly stabilized in the tetramer, but a 1:1 Mad1-Mad2 complex slowly releases Mad2 for Cdc20 binding, driven by favourable binding energies. Thus, the rate of Mad2 binding to Cdc20 during checkpoint activation may be regulated by conformational changes that destabilize the tetrameric Mad1-Mad2 assembly to promote Mad2 release. We also show that unlocking the Mad2 C-terminal tail is required for ligand release from Mad2, and that the 'safety belt' mechanism may prolong the lifetime of Mad2-ligand complexes.

Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a 'safety belt' binding mechanism for the spindle checkpoint.,Sironi L, Mapelli M, Knapp S, De Antoni A, Jeang KT, Musacchio A EMBO J. 2002 May 15;21(10):2496-506. PMID:12006501^[7]

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
↑ Jin DY, Kozak CA, Pangilinan F, Spencer F, Green ED, Jeang KT. Mitotic checkpoint locus MAD1L1 maps to human chromosome 7p22 and mouse chromosome 5. Genomics. 1999 Feb 1;55(3):363-4. PMID:10049595 doi:http://dx.doi.org/10.1006/geno.1998.5654
↑ Lin SY, Elledge SJ. Multiple tumor suppressor pathways negatively regulate telomerase. Cell. 2003 Jun 27;113(7):881-9. PMID:12837246
↑ Nakano H, Funasaka T, Hashizume C, Wong RW. Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis. J Biol Chem. 2010 Apr 2;285(14):10841-9. doi: 10.1074/jbc.M110.105890. Epub 2010 , Feb 4. PMID:20133940 doi:http://dx.doi.org/10.1074/jbc.M110.105890
↑ Sironi L, Mapelli M, Knapp S, De Antoni A, Jeang KT, Musacchio A. Crystal structure of the tetrameric Mad1-Mad2 core complex: implications of a 'safety belt' binding mechanism for the spindle checkpoint. EMBO J. 2002 May 15;21(10):2496-506. PMID:12006501 doi:10.1093/emboj/21.10.2496

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1go4"

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[1go4]] is a 8 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=1GO4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1GO4 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1duj|1duj]]</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]), MAD1L1, MAD1, TXBP181 ([http://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=1go4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1go4 OCA], [http://pdbe.org/1go4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1go4 RCSB], [http://www.ebi.ac.uk/pdbsum/1go4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1go4 ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/MD1L1_HUMAN MD1L1_HUMAN]] Defects in MAD1L1 are involved in the development and/or progression of various types of cancer.
 == 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/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/MD1L1_HUMAN MD1L1_HUMAN]] Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. May recruit MAD2L1 to unattached kinetochores. Has a role in the correct positioning of the septum. Required for anchoring MAD2L1 to the nuclear periphery. Binds to the TERT promoter and represses telomerase expression, possibly by interfering with MYC binding.<ref>PMID:10049595</ref> <ref>PMID:12837246</ref> <ref>PMID:20133940</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/go/1go4_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/go/1go4_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1go4

From Proteopedia

Revision as of 05:58, 20 June 2018

Crystal structure of Mad1-Mad2 reveals a conserved Mad2 binding motif in Mad1 and Cdc20.

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox