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| | <SX load='6f0x' size='340' side='right' viewer='molstar' caption='[[6f0x]], [[Resolution|resolution]] 4.60Å' scene=''> | | <SX load='6f0x' size='340' side='right' viewer='molstar' caption='[[6f0x]], [[Resolution|resolution]] 4.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6f0x]] is a 9 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=6F0X OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6F0X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6f0x]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F0X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6F0X FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRIP13, PCH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CDC20 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MAD2L1, MAD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6f0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f0x OCA], [http://pdbe.org/6f0x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f0x RCSB], [http://www.ebi.ac.uk/pdbsum/6f0x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f0x 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=6f0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f0x OCA], [https://pdbe.org/6f0x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6f0x RCSB], [https://www.ebi.ac.uk/pdbsum/6f0x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6f0x 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/PCH2_HUMAN PCH2_HUMAN]] Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways. Also required for development of higher-order chromosome structures and is needed for synaptonemal-complex formation. In males, required for efficient synapsis of the sex chromosomes and for sex body formation. Promotes early steps of the DNA double-strand breaks (DSBs) repair process upstream of the assembly of RAD51 complexes. Required for depletion of HORMAD1 and HORMAD2 from synapsed chromosomes (By similarity). [[http://www.uniprot.org/uniprot/CDC20_HUMAN CDC20_HUMAN]] Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation.<ref>PMID:9811605</ref> <ref>PMID:9734353</ref> <ref>PMID:9637688</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/PCH2_HUMAN PCH2_HUMAN] Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways. Also required for development of higher-order chromosome structures and is needed for synaptonemal-complex formation. In males, required for efficient synapsis of the sex chromosomes and for sex body formation. Promotes early steps of the DNA double-strand breaks (DSBs) repair process upstream of the assembly of RAD51 complexes. Required for depletion of HORMAD1 and HORMAD2 from synapsed chromosomes (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Alfieri, C]] | + | [[Category: Alfieri C]] |
| - | [[Category: Barford, D]] | + | [[Category: Barford D]] |
| - | [[Category: Chang, L]] | + | [[Category: Chang L]] |
| - | [[Category: Aaa+ atpase]]
| + | |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Chromosome segregation]]
| + | |
| - | [[Category: Mitosis]]
| + | |
| - | [[Category: Remodeller]]
| + | |
| Structural highlights
Function
PCH2_HUMAN Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways. Also required for development of higher-order chromosome structures and is needed for synaptonemal-complex formation. In males, required for efficient synapsis of the sex chromosomes and for sex body formation. Promotes early steps of the DNA double-strand breaks (DSBs) repair process upstream of the assembly of RAD51 complexes. Required for depletion of HORMAD1 and HORMAD2 from synapsed chromosomes (By similarity).
Publication Abstract from PubMed
The maintenance of genome stability during mitosis is coordinated by the spindle assembly checkpoint (SAC) through its effector the mitotic checkpoint complex (MCC), an inhibitor of the anaphase-promoting complex (APC/C, also known as the cyclosome)(1,2). Unattached kinetochores control MCC assembly by catalysing a change in the topology of the beta-sheet of MAD2 (an MCC subunit), thereby generating the active closed MAD2 (C-MAD2) conformer(3-5). Disassembly of free MCC, which is required for SAC inactivation and chromosome segregation, is an ATP-dependent process driven by the AAA+ ATPase TRIP13. In combination with p31(comet), an SAC antagonist(6), TRIP13 remodels C-MAD2 into inactive open MAD2 (O-MAD2)(7-10). Here, we present a mechanism that explains how TRIP13-p31(comet) disassembles the MCC. Cryo-electron microscopy structures of the TRIP13-p31(comet)-C-MAD2-CDC20 complex reveal that p31(comet) recruits C-MAD2 to a defined site on the TRIP13 hexameric ring, positioning the N terminus of C-MAD2 (MAD2(NT)) to insert into the axial pore of TRIP13 and distorting the TRIP13 ring to initiate remodelling. Molecular modelling suggests that by gripping MAD2(NT) within its axial pore, TRIP13 couples sequential ATP-driven translocation of its hexameric ring along MAD2(NT) to push upwards on, and simultaneously rotate, the globular domains of the p31(comet)-C-MAD2 complex. This unwinds a region of the alphaA helix of C-MAD2 that is required to stabilize the C-MAD2 beta-sheet, thus destabilizing C-MAD2 in favour of O-MAD2 and dissociating MAD2 from p31(comet). Our study provides insights into how specific substrates are recruited to AAA+ ATPases through adaptor proteins and suggests a model of how translocation through the axial pore of AAA+ ATPases is coupled to protein remodelling.
Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13.,Alfieri C, Chang L, Barford D Nature. 2018 Jul;559(7713):274-278. doi: 10.1038/s41586-018-0281-1. Epub 2018 Jul, 4. PMID:29973720[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alfieri C, Chang L, Barford D. Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13. Nature. 2018 Jul;559(7713):274-278. doi: 10.1038/s41586-018-0281-1. Epub 2018 Jul, 4. PMID:29973720 doi:http://dx.doi.org/10.1038/s41586-018-0281-1
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