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| | <StructureSection load='6kto' size='340' side='right'caption='[[6kto]], [[Resolution|resolution]] 3.45Å' scene=''> | | <StructureSection load='6kto' size='340' side='right'caption='[[6kto]], [[Resolution|resolution]] 3.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6kto]] is a 4 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=6KTO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KTO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6kto]] is a 4 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=6KTO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KTO FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAD2L2, MAD2B, REV7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SHLD3, FLJ26957, RINN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SHLD2, FAM35A, RINN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4497633Å</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=6kto FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kto OCA], [http://pdbe.org/6kto PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kto RCSB], [http://www.ebi.ac.uk/pdbsum/6kto PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kto 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=6kto FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kto OCA], [https://pdbe.org/6kto PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kto RCSB], [https://www.ebi.ac.uk/pdbsum/6kto PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kto ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MD2L2_HUMAN MD2L2_HUMAN]] Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1. Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation.<ref>PMID:11459825</ref> <ref>PMID:11459826</ref> <ref>PMID:17719540</ref> <ref>PMID:17296730</ref> <ref>PMID:19443654</ref> [[http://www.uniprot.org/uniprot/SHLD2_HUMAN SHLD2_HUMAN]] Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) (PubMed:29656893, PubMed:29789392). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection (PubMed:29656893, PubMed:29789392). Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres (PubMed:29656893).<ref>PMID:29656893</ref> <ref>PMID:29789392</ref> [[http://www.uniprot.org/uniprot/SHLD3_HUMAN SHLD3_HUMAN]] Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection. Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres.<ref>PMID:29656893</ref> | + | [https://www.uniprot.org/uniprot/MD2L2_HUMAN MD2L2_HUMAN] Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1. Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation.<ref>PMID:11459825</ref> <ref>PMID:11459826</ref> <ref>PMID:17719540</ref> <ref>PMID:17296730</ref> <ref>PMID:19443654</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Liang, L]] | + | [[Category: Liang L]] |
| - | [[Category: Yin, Y]] | + | [[Category: Yin Y]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Conformational dimer]]
| + | |
| - | [[Category: Nhej]]
| + | |
| - | [[Category: Replication]]
| + | |
| - | [[Category: Shieldin]]
| + | |
| Structural highlights
Function
MD2L2_HUMAN Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1. Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Shieldin, including SHLD1, SHLD2, SHLD3 and REV7, functions as a bridge linking 53BP1-RIF1 and single-strand DNA to suppress the DNA termini nucleolytic resection during non-homologous end joining (NHEJ). However, the mechanism of shieldin assembly remains unclear. Here we present the crystal structure of the SHLD3-REV7-SHLD2 ternary complex and reveal an unexpected C (closed)-REV7-O (open)-REV7 conformational dimer mediated by SHLD3. We show that SHLD2 interacts with O-REV7 and the N-terminus of SHLD3 by forming beta sheet sandwich. Disruption of the REV7 conformational dimer abolishes the assembly of shieldin and impairs NHEJ efficiency. The conserved FXPWFP motif of SHLD3 binds to C-REV7 and blocks its binding to REV1, which excludes shieldin from the REV1/Pol zeta translesion synthesis (TLS) complex. Our study reveals the molecular architecture of shieldin assembly, elucidates the structural basis of the REV7 conformational dimer, and provides mechanistic insight into orchestration between TLS and NHEJ.
Molecular basis for assembly of the shieldin complex and its implications for NHEJ.,Liang L, Feng J, Zuo P, Yang J, Lu Y, Yin Y Nat Commun. 2020 Apr 24;11(1):1972. doi: 10.1038/s41467-020-15879-5. PMID:32332881[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pfleger CM, Salic A, Lee E, Kirschner MW. Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1. Genes Dev. 2001 Jul 15;15(14):1759-64. PMID:11459825 doi:10.1101/gad.897901
- ↑ Chen J, Fang G. MAD2B is an inhibitor of the anaphase-promoting complex. Genes Dev. 2001 Jul 15;15(14):1765-70. PMID:11459826 doi:10.1101/gad.898701
- ↑ Iwai H, Kim M, Yoshikawa Y, Ashida H, Ogawa M, Fujita Y, Muller D, Kirikae T, Jackson PK, Kotani S, Sasakawa C. A bacterial effector targets Mad2L2, an APC inhibitor, to modulate host cell cycling. Cell. 2007 Aug 24;130(4):611-23. PMID:17719540 doi:10.1016/j.cell.2007.06.043
- ↑ Zhang L, Yang SH, Sharrocks AD. Rev7/MAD2B links c-Jun N-terminal protein kinase pathway signaling to activation of the transcription factor Elk-1. Mol Cell Biol. 2007 Apr;27(8):2861-9. Epub 2007 Feb 12. PMID:17296730 doi:10.1128/MCB.02276-06
- ↑ Hong CF, Chou YT, Lin YS, Wu CW. MAD2B, a novel TCF4-binding protein, modulates TCF4-mediated epithelial-mesenchymal transdifferentiation. J Biol Chem. 2009 Jul 17;284(29):19613-22. doi: 10.1074/jbc.M109.005017. Epub, 2009 May 14. PMID:19443654 doi:10.1074/jbc.M109.005017
- ↑ Liang L, Feng J, Zuo P, Yang J, Lu Y, Yin Y. Molecular basis for assembly of the shieldin complex and its implications for NHEJ. Nat Commun. 2020 Apr 24;11(1):1972. doi: 10.1038/s41467-020-15879-5. PMID:32332881 doi:http://dx.doi.org/10.1038/s41467-020-15879-5
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