4zrj

From Proteopedia

(Difference between revisions)

Revision as of 13:26, 19 April 2017

Structure of Merlin-FERM and CTD

Structural highlights

4zrj is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4zri, 4zrk
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MERL_HUMAN] Neurofibromatosis type 3;Neurofibromatosis type 2. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry.

Function

[MERL_HUMAN] 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.^[1] ^[2]

Publication Abstract from PubMed

The tumor suppressor Merlin/NF2 functions upstream of the core Hippo pathway kinases Lats1/2 and Mst1/2, as well as the nuclear E3 ubiquitin ligase CRL4DCAF1. Numerous mutations of Merlin have been identified in Neurofibromatosis type 2 and other cancer patients. Despite more than two decades of research, the upstream regulator of Merlin in the Hippo pathway remains unknown. Here we show by high-resolution crystal structures that the Lats1/2-binding site on the Merlin FERM domain is physically blocked by Merlin's auto-inhibitory tail. Angiomotin binding releases the auto-inhibition and promotes Merlin's binding to Lats1/2. Phosphorylation of Ser518 outside the Merlin's auto-inhibitory tail does not obviously alter Merlin's conformation, but instead prevents angiomotin from binding and thus inhibits Hippo pathway kinase activation. Cancer-causing mutations clustered in the angiomotin-binding domain impair angiomotin-mediated Merlin activation. Our findings reveal that angiomotin and Merlin respectively interface cortical actin filaments and core kinases in Hippo signaling, and allow construction of a complete Hippo signaling pathway.Cell Research advance online publication 5 June 2015; doi: 10.1038/cr.2015.69.

Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway.,Li Y, Zhou H, Li F, Chan SW, Lin Z, Wei Z, Yang Z, Guo F, Lim CJ, Xing W, Shen Y, Hong W, Long J, Zhang M Cell Res. 2015 Jun 5. doi: 10.1038/cr.2015.69. PMID:26045165^[3]

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

References

↑ Li W, You L, Cooper J, Schiavon G, Pepe-Caprio A, Zhou L, Ishii R, Giovannini M, Hanemann CO, Long SB, Erdjument-Bromage H, Zhou P, Tempst P, Giancotti FG. Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell. 2010 Feb 19;140(4):477-90. doi: 10.1016/j.cell.2010.01.029. PMID:20178741 doi:http://dx.doi.org/10.1016/j.cell.2010.01.029
↑ Yu J, Zheng Y, Dong J, Klusza S, Deng WM, Pan D. Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded. Dev Cell. 2010 Feb 16;18(2):288-99. doi: 10.1016/j.devcel.2009.12.012. PMID:20159598 doi:http://dx.doi.org/10.1016/j.devcel.2009.12.012
↑ Li Y, Zhou H, Li F, Chan SW, Lin Z, Wei Z, Yang Z, Guo F, Lim CJ, Xing W, Shen Y, Hong W, Long J, Zhang M. Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway. Cell Res. 2015 Jun 5. doi: 10.1038/cr.2015.69. PMID:26045165 doi:http://dx.doi.org/10.1038/cr.2015.69

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4zrj"

@@ Line 1: / Line 1: @@
 ==Structure of Merlin-FERM and CTD==
 <StructureSection load='4zrj' size='340' side='right' caption='[[4zrj]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zri|4zri]], [[4zrk|4zrk]]</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=4zrj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zrj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zrj RCSB], [http://www.ebi.ac.uk/pdbsum/4zrj PDBsum]</span></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=4zrj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zrj OCA], [http://pdbe.org/4zrj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zrj RCSB], [http://www.ebi.ac.uk/pdbsum/4zrj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zrj ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4zrj" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4zrj

From Proteopedia

Revision as of 13:26, 19 April 2017

Structure of Merlin-FERM and CTD

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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