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4bld

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Revision as of 13:42, 13 March 2019

Crystal structure of a human Suppressor of fused (SUFU)-GLI3p complex

Structural highlights

4bld is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4bl8, 4bl9, 4bla, 4blb
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[GLI3_HUMAN] Postaxial polydactyly type B, unilateral;Postaxial polydactyly type A, unilateral;Pallister-Hall syndrome;Postaxial polydactyly type A, bilateral;Polysyndactyly, bilateral;Polysyndactyly, unilateral;Greig cephalopolysyndactyly syndrome;Acrocallosal syndrome;Postaxial polydactyly type B, bilateral. 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 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 is caused by mutations affecting the gene represented in this entry.

Function

[MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. [GLI3_HUMAN] Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development. The full-length GLI3 form (GLI3FL) after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor. A proper balance between the GLI3 activator and the repressor GLI3R, rather than the repressor gradient itself or the activator/repressor ratio gradient, specifies limb digit number and identity. In concert with TRPS1, plays a role in regulating the size of the zone of distal chondrocytes, in restricting the zone of PTHLH expression in distal cells and in activating chondrocyte proliferation. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU-GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU-GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics.

Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation.,Cherry AL, Finta C, Karlstrom M, Jin Q, Schwend T, Astorga-Wells J, Zubarev RA, Del Campo M, Criswell AR, de Sanctis D, Jovine L, Toftgard R Acta Crystallogr D Biol Crystallogr. 2013 Dec;69(Pt 12):2563-79. doi:, 10.1107/S0907444913028473. Epub 2013 Nov 19. PMID:24311597^[4]

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

References

↑ Wang B, Fallon JF, Beachy PA. Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb. Cell. 2000 Feb 18;100(4):423-34. PMID:10693759
↑ Koyabu Y, Nakata K, Mizugishi K, Aruga J, Mikoshiba K. Physical and functional interactions between Zic and Gli proteins. J Biol Chem. 2001 Mar 9;276(10):6889-92. Epub 2001 Jan 12. PMID:11238441 doi:http://dx.doi.org/10.1074/jbc.C000773200
↑ Zhu L, Zhou G, Poole S, Belmont JW. Characterization of the interactions of human ZIC3 mutants with GLI3. Hum Mutat. 2008 Jan;29(1):99-105. PMID:17764085 doi:10.1002/humu.20606
↑ Cherry AL, Finta C, Karlstrom M, Jin Q, Schwend T, Astorga-Wells J, Zubarev RA, Del Campo M, Criswell AR, de Sanctis D, Jovine L, Toftgard R. Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation. Acta Crystallogr D Biol Crystallogr. 2013 Dec;69(Pt 12):2563-79. doi:, 10.1107/S0907444913028473. Epub 2013 Nov 19. PMID:24311597 doi:http://dx.doi.org/10.1107/S0907444913028473

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/4bld"

@@ Line 1: / Line 1: @@
 ==Crystal structure of a human Suppressor of fused (SUFU)-GLI3p complex==
-<StructureSection load='4bld' size='340' side='right' caption='[[4bld]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='4bld' size='340' side='right'caption='[[4bld]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4bld]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BLD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BLD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4bld]] is a 8 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=4BLD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BLD FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MAL:MALTOSE'>MAL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bl8|4bl8]], [[4bl9|4bl9]], [[4bla|4bla]], [[4blb|4blb]]</td></tr>
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Cherry, A L]]
 [[Category: Finta, C]]

4bld

From Proteopedia

Revision as of 13:42, 13 March 2019

Crystal structure of a human Suppressor of fused (SUFU)-GLI3p complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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