5xpt

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of MAD2L2/REV7 in complex with a CAMP fragment in a tetragonal crystal

Structural highlights

5xpt is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.102Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Mitotic arrest deficient 2-like protein 2 (MAD2L2), also termed MAD2B or REV7, is involved in multiple cellular functions including translesion DNA synthesis (TLS), signal transduction, transcription, and mitotic events. MAD2L2 interacts with chromosome alignment-maintaining phosphoprotein (CAMP), a kinetochore-microtubule attachment protein in mitotic cells, presumably through a novel "WK" motif in CAMP. Structures of MAD2L2 in complex with binding regions of the TLS proteins REV3 and REV1 have revealed that MAD2L2 has two faces for protein-protein interactions (PPIs) that are regulated by its C-terminal region; however, the mechanisms underlying the MAD2L2-CAMP interaction and the mitotic role of MAD2L2 remain unknown. Here we have determined the structures of human MAD2L2 in complex with a CAMP fragment in two crystal forms. The overall structure of the MAD2L2-CAMP complex in both crystal forms was essentially similar to that of the MAD2L2-REV3 complex. However, the residue interactions between MAD2L2 and CAMP were strikingly different from those in the MAD2L2-REV3 complex. Furthermore, structure-based interaction analyses revealed an unprecedented mechanism involving CAMP's WK motif. Surprisingly, in one of the crystal forms, the MAD2L2-CAMP complex formed a dimeric structure in which the C-terminal region of MAD2L2 was swapped and adopted an immature structure. The structure provides direct evidence for the dynamic nature of MAD2L2 structure, which in turn may have implications for the PPI mechanism and the multiple functions of this protein. This work is the first structural study of MAD2L2 aside from its role in TLS and might pave the way to clarify MAD2L2's function in mitosis.

Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment maintaining phosphoprotein (CAMP).,Hara K, Taharazako S, Ikeda M, Fujita H, Mikami Y, Kikuchi S, Hishiki A, Yokoyama H, Ishikawa Y, Kanno SI, Tanaka K, Hashimoto H J Biol Chem. 2017 Sep 8. pii: jbc.M117.804237. doi: 10.1074/jbc.M117.804237. PMID:28887307^[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
↑ Hara K, Taharazako S, Ikeda M, Fujita H, Mikami Y, Kikuchi S, Hishiki A, Yokoyama H, Ishikawa Y, Kanno SI, Tanaka K, Hashimoto H. Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment maintaining phosphoprotein (CAMP). J Biol Chem. 2017 Sep 8. pii: jbc.M117.804237. doi: 10.1074/jbc.M117.804237. PMID:28887307 doi:http://dx.doi.org/10.1074/jbc.M117.804237

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5xpt"

Categories: Homo sapiens | Large Structures | Hara K | Hashimoto H | Taharazako S

@@ Line 1: / Line 1: @@
 ==Crystal structure of MAD2L2/REV7 in complex with a CAMP fragment in a tetragonal crystal==
-<StructureSection load='5xpt' size='340' side='right' caption='[[5xpt]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='5xpt' size='340' side='right'caption='[[5xpt]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xpt]] is a 2 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=5XPT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XPT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xpt]] is a 2 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=5XPT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XPT 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]), CHAMP1, C13orf8, CAMP, CHAMP, KIAA1802, ZNF828 ([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]] 2.102&#8491;</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=5xpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xpt OCA], [http://pdbe.org/5xpt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xpt RCSB], [http://www.ebi.ac.uk/pdbsum/5xpt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xpt 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=5xpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xpt OCA], [https://pdbe.org/5xpt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xpt RCSB], [https://www.ebi.ac.uk/pdbsum/5xpt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xpt ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/CHAP1_HUMAN CHAP1_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry.
 == 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/CHAP1_HUMAN CHAP1_HUMAN]] Required for proper alignment of chromosomes at metaphase and their accurate segregation during mitosis. Involved in the maintenance of spindle microtubules attachment to the kinetochore during sister chromatid biorientation. May recruit CENPE and CENPF to the kinetochore.<ref>PMID:21063390</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;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Hara, K]]
+[[Category: Large Structures]]
-[[Category: Hashimoto, H]]
+[[Category: Hara K]]
-[[Category: Taharazako, S]]
+[[Category: Hashimoto H]]
-[[Category: Camp]]
+[[Category: Taharazako S]]
-[[Category: Champ1]]
-[[Category: Mad2b]]
-[[Category: Mad2l2]]
-[[Category: Rev7]]
-[[Category: Transcription-metal binding protein complex]]

5xpt

From Proteopedia

Current revision

Crystal structure of MAD2L2/REV7 in complex with a CAMP fragment in a tetragonal crystal

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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