1h4r

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of the FERM domain of Merlin, the Neurofibromatosis 2 Tumor Suppressor Protein.

Structural highlights

1h4r is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:
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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Neurofibromatosis type 2 is an autosomal dominant disorder characterized by central nervous system tumors. The cause of the disease has been traced to mutations in the gene coding for a protein that is alternately called merlin or schwannomin and is a member of the ERM family (ezrin, radixin and moesin). The ERM proteins link the cytoskeleton to the cell membrane either directly through integral membrane proteins or indirectly through membrane-associated proteins. In this paper, the expression, purification, crystallization and crystal structure of the N-terminal domain of merlin are described. The crystals exhibit the symmetry of space group P2(1)2(1)2(1), with two molecules in the asymmetric unit. The recorded diffraction pattern extends to 1.8A resolution. The structure was solved by the molecular-replacement method and the model was refined to a conventional R value of 19.3% (R(free) = 22.7%). The N-terminal domain of merlin closely resembles those described for the corresponding domains in moesin and radixin and exhibits a cloverleaf architecture with three distinct subdomains. The structure allows a better rationalization of the impact of selected disease-causing mutations on the integrity of the protein.

The structure of the FERM domain of merlin, the neurofibromatosis type 2 gene product.,Kang BS, Cooper DR, Devedjiev Y, Derewenda U, Derewenda ZS Acta Crystallogr D Biol Crystallogr. 2002 Mar;58(Pt 3):381-91. Epub 2002, Feb 21. PMID:11856822^[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
↑ Kang BS, Cooper DR, Devedjiev Y, Derewenda U, Derewenda ZS. The structure of the FERM domain of merlin, the neurofibromatosis type 2 gene product. Acta Crystallogr D Biol Crystallogr. 2002 Mar;58(Pt 3):381-91. Epub 2002, Feb 21. PMID:11856822

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1h4r"

@@ Line 3: / Line 3: @@
 <StructureSection load='1h4r' size='340' side='right'caption='[[1h4r]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1h4r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H4R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H4R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1h4r]] is a 2 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=1H4R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H4R FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1h4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h4r OCA], [https://pdbe.org/1h4r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h4r RCSB], [https://www.ebi.ac.uk/pdbsum/1h4r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h4r ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[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 ==
+[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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Cooper, D R]]
+[[Category: Cooper DR]]
-[[Category: Derewenda, Z S]]
+[[Category: Derewenda ZS]]
-[[Category: Devedjiev, Y]]
+[[Category: Devedjiev Y]]
-[[Category: Kang, B S]]
+[[Category: Kang BS]]
-[[Category: Sheffield, P]]
+[[Category: Sheffield P]]
-[[Category: Anti-oncogene]]
-[[Category: Cytoskeleton]]
-[[Category: Ferm]]
-[[Category: Neurofibromatosis]]
-[[Category: Nf2]]
-[[Category: Structural protein]]

1h4r

From Proteopedia

Current revision

Crystal Structure of the FERM domain of Merlin, the Neurofibromatosis 2 Tumor Suppressor Protein.

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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