4zri

From Proteopedia

(Difference between revisions)

Revision as of 07:38, 18 May 2023

Crystal structure of Merlin-FERM and Lats2

Structural highlights

4zri is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='4zri' size='340' side='right'caption='[[4zri]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4zri]] is a 4 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=4ZRI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZRI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4zri]] is a 4 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=4ZRI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZRI FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zrj|4zrj]], [[4zrk|4zrk]]</td></tr>
+</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=4zri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zri OCA], [https://pdbe.org/4zri PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zri RCSB], [https://www.ebi.ac.uk/pdbsum/4zri PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zri ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NF2, SCH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), LATS2, KPM ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zri OCA], [http://pdbe.org/4zri PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zri RCSB], [http://www.ebi.ac.uk/pdbsum/4zri PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zri ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/MERL_HUMAN 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.
+[https://www.uniprot.org/uniprot/MERL_HUMAN 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 ==
-[[http://www.uniprot.org/uniprot/MERL_HUMAN 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.<ref>PMID:20178741</ref> <ref>PMID:20159598</ref>  [[http://www.uniprot.org/uniprot/LATS2_HUMAN LATS2_HUMAN]] Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability. Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity. Negative regulator of the androgen receptor. Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities. This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ.<ref>PMID:10871863</ref> <ref>PMID:12853976</ref> <ref>PMID:15131260</ref> <ref>PMID:18158288</ref> <ref>PMID:21952048</ref>
+[https://www.uniprot.org/uniprot/MERL_HUMAN 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.<ref>PMID:20178741</ref> <ref>PMID:20159598</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Li, F]]
+[[Category: Li F]]
-[[Category: Long, J]]
+[[Category: Long J]]
-[[Category: Shen, Y]]
+[[Category: Shen Y]]
-[[Category: Zhou, H]]
+[[Category: Zhou H]]
-[[Category: Ferm]]
-[[Category: Lats2]]
-[[Category: Merlin]]
-[[Category: Signaling protein-transferase complex]]

4zri

From Proteopedia

Revision as of 07:38, 18 May 2023

Crystal structure of Merlin-FERM and Lats2

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

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