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4p7i

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Crystal structure of the Merlin FERM/DCAF1 complex

Structural highlights

4p7i is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

Publication Abstract from PubMed

The tumor suppressor gene Nf2 product, Merlin, plays vital roles in controlling proper development of organ sizes by specifically binding to a large number of target proteins localized both in cytoplasm and nuclei. The FERM domain of Merlin is chiefly responsible for its binding to target proteins, although the molecular basis governing these interactions are poorly understood due to lack of structural information. Here we report the crystal structure of the Merlin FERM domain in complex with its binding domain derived from the E3 ubiquitin ligase substrate adaptor DCAF1 (also known as VPRBP). Unlike target binding modes found in ERM proteins, the Merlin-FERM binding domain of DCAF1 folds as a beta-hairpin and binds to the alpha1/beta5-groove of the F3 lobe of Merlin-FERM via extensive hydrophobic interactions. In addition to providing the first structural glimpse of a Merlin-FERM/target complex, the structure of the Merlin/DCAF1 complex is likely to be valuable for understanding Merlin's interactions with its binding partners other than DCAF1.

Structural Basis of the Binding of Merlin FERM Domain to the E3 Ubiquitin Ligase Substrate Adaptor DCAF1.,Li Y, Wei Z, Zhang J, Yang Z, Zhang M J Biol Chem. 2014 Apr 4. PMID:24706749^[2]

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

References

↑ Wiley LA, Dattilo LK, Kang KB, Giovannini M, Beebe DC. The tumor suppressor merlin is required for cell cycle exit, terminal differentiation, and cell polarity in the developing murine lens. Invest Ophthalmol Vis Sci. 2010 Jul;51(7):3611-8. doi: 10.1167/iovs.09-4371. Epub, 2010 Feb 24. PMID:20181838 doi:http://dx.doi.org/10.1167/iovs.09-4371
↑ Li Y, Wei Z, Zhang J, Yang Z, Zhang M. Structural Basis of the Binding of Merlin FERM Domain to the E3 Ubiquitin Ligase Substrate Adaptor DCAF1. J Biol Chem. 2014 Apr 4. PMID:24706749 doi:http://dx.doi.org/10.1074/jbc.M114.551184

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4p7i"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4p7i]] is a 4 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=4P7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P7I FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4p7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p7i OCA], [https://pdbe.org/4p7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p7i RCSB], [https://www.ebi.ac.uk/pdbsum/4p7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p7i ProSAT]</span></td></tr>
 </table>

4p7i

From Proteopedia

Current revision

Crystal structure of the Merlin FERM/DCAF1 complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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