View source for 4zrk


==Merlin-FERM and Lats1 complex==
<StructureSection load='4zrk' size='340' side='right'caption='[[4zrk]], [[Resolution|resolution]] 2.32&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zrk]] is a 8 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=4ZRK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZRK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.316&#8491;</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=4zrk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zrk OCA], [https://pdbe.org/4zrk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zrk RCSB], [https://www.ebi.ac.uk/pdbsum/4zrk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zrk ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:26045165</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zrk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Merlin|Merlin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Li Y]]
[[Category: Lin Z]]
[[Category: Wei Z]]
[[Category: Zhang M]]