4km8

From Proteopedia

(Difference between revisions)

Revision as of 08:09, 5 August 2016

Crystal structure of Sufud60

Structural highlights

4km8 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	4km9, 4kma, 4kmd, 4kmh
Gene:	SUFU, UNQ650/PRO1280 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SUFU_HUMAN] Defects in SUFU are a cause of medulloblastoma (MDB) [MIM:155255]. MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. Defects in SUFU play a role in predisposition to desmoplastic MDB. These tumors make up about 20 to 30% of medulloblastomas, have a more nodular architecture than 'classical' medulloblastoma, and may have a better prognosis.

Function

[SUFU_HUMAN] Negative regulator in the hedgehog signaling pathway. Down-regulates GLI1-mediated transactivation of target genes. Part of a corepressor complex that acts on DNA-bound GLI1. May also act by linking GLI1 to BTRC and thereby targeting GLI1 to degradation by the proteasome. Sequesters GLI1, GLI2 and GLI3 in the cytoplasm, this effect is overcome by binding of STK36 to both SUFU and a GLI protein. Negative regulator of beta-catenin signaling. Regulates the formation of either the repressor form (GLI3R) or the activator form (GLI3A) of the full length form of GLI3 (GLI3FL). GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. When Hh signaling is initiated, SUFU dissociates from GLI3FL and the latter translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A).^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Hedgehog (Hh) signalling regulates embryonic development and adult tissue homoeostasis. Mutations of its pathway components including Suppressor of Fused (Sufu) and Gli/Ci predispose to cancers and congenital anomalies. The Sufu-Gli protein complex occupies a central position in the vertebrate Hh signalling pathway, especially in mammals. Here structures of full-length human and Drosophila Sufu, the human Sufu-Gli complex, along with normal mode analysis and FRET measurement results, reveal that Sufu alternates between 'open' and 'closed' conformations. The 'closed' form of Sufu is stabilized by Gli binding and inhibited by Hh treatment, whereas the 'open' state of Sufu is promoted by Gli-dissociation and Hh signalling. Mutations of critical interface residues disrupt the Sufu-Gli complex and prevent Sufu from repressing Gli-mediated transcription, tethering Gli in the cytoplasm and protecting Gli from the 26S proteasome-mediated degradation. Our study thus provides mechanistic insight into the mutual recognition and regulation between Sufu and Gli/Ci.

Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci.,Zhang Y, Fu L, Qi X, Zhang Z, Xia Y, Jia J, Jiang J, Zhao Y, Wu G Nat Commun. 2013;4:2608. doi: 10.1038/ncomms3608. PMID:24217340^[6]

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

References

↑ Stone DM, Murone M, Luoh S, Ye W, Armanini MP, Gurney A, Phillips H, Brush J, Goddard A, de Sauvage FJ, Rosenthal A. Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli. J Cell Sci. 1999 Dec;112 ( Pt 23):4437-48. PMID:10564661
↑ Kogerman P, Grimm T, Kogerman L, Krause D, Unden AB, Sandstedt B, Toftgard R, Zaphiropoulos PG. Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1. Nat Cell Biol. 1999 Sep;1(5):312-9. PMID:10559945 doi:10.1038/13031
↑ Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG, Zhang X, Agatep R, Chiappa S, Gao L, Lowrance A, Hao A, Goldstein AM, Stavrou T, Scherer SW, Dura WT, Wainwright B, Squire JA, Rutka JT, Hogg D. Mutations in SUFU predispose to medulloblastoma. Nat Genet. 2002 Jul;31(3):306-10. Epub 2002 Jun 17. PMID:12068298 doi:10.1038/ng916
↑ Murone M, Luoh SM, Stone D, Li W, Gurney A, Armanini M, Grey C, Rosenthal A, de Sauvage FJ. Gli regulation by the opposing activities of fused and suppressor of fused. Nat Cell Biol. 2000 May;2(5):310-2. PMID:10806483 doi:10.1038/35010610
↑ Chi S, Xie G, Liu H, Chen K, Zhang X, Li C, Xie J. Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-dependent manner. Cell Signal. 2012 Jun;24(6):1222-8. doi: 10.1016/j.cellsig.2012.02.004. Epub 2012, Feb 18. PMID:22365972 doi:10.1016/j.cellsig.2012.02.004
↑ Zhang Y, Fu L, Qi X, Zhang Z, Xia Y, Jia J, Jiang J, Zhao Y, Wu G. Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci. Nat Commun. 2013;4:2608. doi: 10.1038/ncomms3608. PMID:24217340 doi:http://dx.doi.org/10.1038/ncomms3608

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/4km8"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Sufud60==
 <StructureSection load='4km8' size='340' side='right' caption='[[4km8]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4km9|4km9]], [[4kma|4kma]], [[4kmd|4kmd]], [[4kmh|4kmh]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SUFU, UNQ650/PRO1280 ([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=4km8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4km8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4km8 RCSB], [http://www.ebi.ac.uk/pdbsum/4km8 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=4km8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4km8 OCA], [http://pdbe.org/4km8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4km8 RCSB], [http://www.ebi.ac.uk/pdbsum/4km8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4km8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4km8" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4km8

From Proteopedia

Revision as of 08:09, 5 August 2016

Crystal structure of Sufud60

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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