3u8z

From Proteopedia

(Difference between revisions)

Revision as of 10:18, 4 January 2015

human merlin FERM domain

Structural highlights

3u8z 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.
Gene:	NF2, SCH (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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 merlin-1 tumor suppressor is encoded by the Neurofibromatosis-2 (Nf2) gene and loss-of-function Nf2 mutations lead to nervous system tumors in man and to several tumor types in mice. Merlin is an ERM (ezrin, radixin, moesin) family cytoskeletal protein that interacts with other ERM proteins and with components of cell-cell adherens junctions (AJs). Merlin stabilizes the links of AJs to the actin cytoskeleton. Thus, its loss destabilizes AJs, promoting cell migration and invasion, which in Nf2(+/-) mice leads to highly metastatic tumors. Paradoxically, the 'closed' conformation of merlin-1, where its N-terminal four-point-one, ezrin, radixin, moesin (FERM) domain binds to its C-terminal tail domain, directs its tumor suppressor functions. Here we report the crystal structure of the human merlin-1 head domain when crystallized in the presence of its tail domain. Remarkably, unlike other ERM head-tail interactions, this structure suggests that binding of the tail provokes dimerization and dynamic movement and unfurling of the F2 motif of the FERM domain. We conclude the 'closed' tumor suppressor conformer of merlin-1 is in fact an 'open' dimer whose functions are disabled by Nf2 mutations that disrupt this architecture.

Unfurling of the band 4.1, ezrin, radixin, moesin (FERM) domain of the merlin tumor suppressor.,Yogesha SD, Sharff AJ, Giovannini M, Bricogne G, Izard T Protein Sci. 2011 Oct 19. doi: 10.1002/pro.751. PMID:22012890^[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
↑ Yogesha SD, Sharff AJ, Giovannini M, Bricogne G, Izard T. Unfurling of the band 4.1, ezrin, radixin, moesin (FERM) domain of the merlin tumor suppressor. Protein Sci. 2011 Oct 19. doi: 10.1002/pro.751. PMID:22012890 doi:10.1002/pro.751

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/3u8z"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3u8z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U8Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U8Z FirstGlance]. <br>
-</td></tr><tr><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 Homo sapiens])</td></tr>
+</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 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3u8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u8z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3u8z RCSB], [http://www.ebi.ac.uk/pdbsum/3u8z 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=3u8z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u8z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3u8z RCSB], [http://www.ebi.ac.uk/pdbsum/3u8z PDBsum]</span></td></tr>
-<table>
+</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.
@@ Line 16: / Line 16: @@
 Unfurling of the band 4.1, ezrin, radixin, moesin (FERM) domain of the merlin tumor suppressor.,Yogesha SD, Sharff AJ, Giovannini M, Bricogne G, Izard T Protein Sci. 2011 Oct 19. doi: 10.1002/pro.751. PMID:22012890<ref>PMID:22012890</ref>
-From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
 == References ==
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bricogne, G.]]
+[[Category: Bricogne, G]]
-[[Category: Giovannini, M.]]
+[[Category: Giovannini, M]]
-[[Category: Izard, T.]]
+[[Category: Izard, T]]
-[[Category: Sharff, A J.]]
+[[Category: Sharff, A J]]
-[[Category: Yogesha, S D.]]
+[[Category: Yogesha, S D]]
 [[Category: Neurofibromatosis]]
 [[Category: Signaling protein]]
 [[Category: Tumor suppressor]]

3u8z

From Proteopedia

Revision as of 10:18, 4 January 2015

human merlin FERM domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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