4p7i

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{{STRUCTURE_4p7i| PDB=4p7i | SCENE= }}
 
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===Crystal structure of the Merlin FERM/DCAF1 complex===
 
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==Function==
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==Crystal structure of the Merlin FERM/DCAF1 complex==
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[[http://www.uniprot.org/uniprot/MERL_MOUSE MERL_MOUSE]] Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex (By similarity). Plays a role in lens development and is required for complete fiber cell terminal differentiation, maintenance of cell polarity and separation of the lens vesicle from the corneal epithelium.<ref>PMID:20181838</ref> [[http://www.uniprot.org/uniprot/VPRBP_HUMAN VPRBP_HUMAN]] Component of the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex, VprBP/DCAF1 may function as the substrate recognition module within this complex. For example, VprBP/DCAF1 targets NF2 to the E3 ubiquitin-ligase complex for ubiquitination and subsequent proteasome-dependent degradation. In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1 function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1 function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage. Associated with chromatin in a DDB1-independent and cell cycle-dependent manner, VprBP/DCAF1 is recruited to chromatin as DNA is being replicated and is released from chromatin before mitosis.<ref>PMID:17314515</ref> <ref>PMID:17620334</ref> <ref>PMID:17626091</ref> <ref>PMID:17630831</ref> <ref>PMID:17609381</ref> <ref>PMID:17559673</ref> <ref>PMID:18524771</ref> <ref>PMID:18606781</ref> <ref>PMID:18332868</ref> <ref>PMID:18464893</ref> <ref>PMID:19264781</ref> <ref>PMID:19923175</ref> <ref>PMID:23063525</ref>
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<StructureSection load='4p7i' size='340' side='right'caption='[[4p7i]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4p7i]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P7I FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4p7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7i OCA], [https://pdbe.org/4p7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p7i RCSB], [https://www.ebi.ac.uk/pdbsum/4p7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p7i ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MERL_MOUSE MERL_MOUSE] Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex (By similarity). Plays a role in lens development and is required for complete fiber cell terminal differentiation, maintenance of cell polarity and separation of the lens vesicle from the corneal epithelium.<ref>PMID:20181838</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The tumor suppressor gene Nf2 product, Merlin, plays vital roles in controlling proper development of organ sizes by specifically binding to a large number of target proteins localized both in cytoplasm and nuclei. The FERM domain of Merlin is chiefly responsible for its binding to target proteins, although the molecular basis governing these interactions are poorly understood due to lack of structural information. Here we report the crystal structure of the Merlin FERM domain in complex with its binding domain derived from the E3 ubiquitin ligase substrate adaptor DCAF1 (also known as VPRBP). Unlike target binding modes found in ERM proteins, the Merlin-FERM binding domain of DCAF1 folds as a beta-hairpin and binds to the alpha1/beta5-groove of the F3 lobe of Merlin-FERM via extensive hydrophobic interactions. In addition to providing the first structural glimpse of a Merlin-FERM/target complex, the structure of the Merlin/DCAF1 complex is likely to be valuable for understanding Merlin's interactions with its binding partners other than DCAF1.
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==About this Structure==
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Structural Basis of the Binding of Merlin FERM Domain to the E3 Ubiquitin Ligase Substrate Adaptor DCAF1.,Li Y, Wei Z, Zhang J, Yang Z, Zhang M J Biol Chem. 2014 Apr 4. PMID:24706749<ref>PMID:24706749</ref>
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[[4p7i]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P7I OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<references group="xtra"/><references/>
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</div>
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[[Category: Non-specific serine/threonine protein kinase]]
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<div class="pdbe-citations 4p7i" style="background-color:#fffaf0;"></div>
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[[Category: Li, Y.]]
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[[Category: Wei, Z.]]
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==See Also==
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[[Category: Zhang, M.]]
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*[[Merlin|Merlin]]
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[[Category: Signaling protein-protein binding complex]]
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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*[[VprBP|VprBP]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Mus musculus]]
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[[Category: Li Y]]
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[[Category: Wei Z]]
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[[Category: Zhang M]]

Current revision

Crystal structure of the Merlin FERM/DCAF1 complex

PDB ID 4p7i

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