2m6n

From Proteopedia

(Difference between revisions)

Revision as of 13:31, 22 February 2023

3D solution structure of EMI1 (Early Mitotic Inhibitor 1)

Structural highlights

2m6n is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FBX5_HUMAN Regulates progression through early mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Binds to the APC activators CDC20 and FZR1/CDH1 to prevent APC activation. Can also bind directly to the APC to inhibit substrate-binding.^[1] ^[2]

Publication Abstract from PubMed

The anaphase-promoting complex/cyclosome (APC/C) is a ~1.5-MDa multiprotein E3 ligase enzyme that regulates cell division by promoting timely ubiquitin-mediated proteolysis of key cell-cycle regulatory proteins. Inhibition of human APC/CCDH1 during interphase by early mitotic inhibitor 1 (EMI1) is essential for accurate coordination of DNA synthesis and mitosis. Here, we report a hybrid structural approach involving NMR, electron microscopy and enzymology, which reveal that EMI1's 143-residue C-terminal domain inhibits multiple APC/CCDH1 functions. The intrinsically disordered D-box, linker and tail elements, together with a structured zinc-binding domain, bind distinct regions of APC/CCDH1 to synergistically both block the substrate-binding site and inhibit ubiquitin-chain elongation. The functional importance of intrinsic structural disorder is explained by enabling a small inhibitory domain to bind multiple sites to shut down various functions of a 'molecular machine' nearly 100 times its size.

Electron microscopy structure of human APC/C-EMI1 reveals multimodal mechanism of E3 ligase shutdown.,Frye JJ, Brown NG, Petzold G, Watson ER, Grace CR, Nourse A, Jarvis MA, Kriwacki RW, Peters JM, Stark H, Schulman BA Nat Struct Mol Biol. 2013 May 26. doi: 10.1038/nsmb.2593. PMID:23708605^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hsu JY, Reimann JD, Sorensen CS, Lukas J, Jackson PK. E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1). Nat Cell Biol. 2002 May;4(5):358-66. PMID:11988738 doi:10.1038/ncb785
↑ Miller JJ, Summers MK, Hansen DV, Nachury MV, Lehman NL, Loktev A, Jackson PK. Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor. Genes Dev. 2006 Sep 1;20(17):2410-20. Epub 2006 Aug 18. PMID:16921029 doi:gad.1454006
↑ Frye JJ, Brown NG, Petzold G, Watson ER, Grace CR, Nourse A, Jarvis MA, Kriwacki RW, Peters JM, Stark H, Schulman BA. Electron microscopy structure of human APC/C-EMI1 reveals multimodal mechanism of E3 ligase shutdown. Nat Struct Mol Biol. 2013 May 26. doi: 10.1038/nsmb.2593. PMID:23708605 doi:10.1038/nsmb.2593

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/2m6n"

@@ Line 1: / Line 1: @@
 ==3D solution structure of EMI1 (Early Mitotic Inhibitor 1)==
-<StructureSection load='2m6n' size='340' side='right'caption='[[2m6n]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2m6n' size='340' side='right'caption='[[2m6n]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2m6n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M6N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M6N FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2m6n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M6N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M6N FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ct7|2ct7]], [[2jmo|2jmo]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FBXO5, EMI1, FBX5 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=2m6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m6n OCA], [https://pdbe.org/2m6n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m6n RCSB], [https://www.ebi.ac.uk/pdbsum/2m6n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m6n ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/FBX5_HUMAN FBX5_HUMAN]] Regulates progression through early mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Binds to the APC activators CDC20 and FZR1/CDH1 to prevent APC activation. Can also bind directly to the APC to inhibit substrate-binding.<ref>PMID:11988738</ref> <ref>PMID:16921029</ref>
+[https://www.uniprot.org/uniprot/FBX5_HUMAN FBX5_HUMAN] Regulates progression through early mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Binds to the APC activators CDC20 and FZR1/CDH1 to prevent APC activation. Can also bind directly to the APC to inhibit substrate-binding.<ref>PMID:11988738</ref> <ref>PMID:16921029</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Brown, N G]]
+[[Category: Brown NG]]
-[[Category: Frye, J J]]
+[[Category: Frye JJ]]
-[[Category: Jarvis, M]]
+[[Category: Jarvis M]]
-[[Category: Kriwacki, R W]]
+[[Category: Kriwacki RW]]
-[[Category: Nourse, A]]
+[[Category: Nourse A]]
-[[Category: Peters, J]]
+[[Category: Peters J]]
-[[Category: Petzold, G]]
+[[Category: Petzold G]]
-[[Category: Royappa, G R]]
+[[Category: Royappa GR]]
-[[Category: Schulman, B A]]
+[[Category: Schulman BA]]
-[[Category: Stark, H]]
+[[Category: Stark H]]
-[[Category: Watson, E R]]
+[[Category: Watson ER]]
-[[Category: Apc]]
-[[Category: Cell cycle]]
-[[Category: E3 ligase]]
-[[Category: Emi1]]
-[[Category: Zbr]]

2m6n

From Proteopedia

Revision as of 13:31, 22 February 2023

3D solution structure of EMI1 (Early Mitotic Inhibitor 1)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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