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| | <StructureSection load='4bld' size='340' side='right'caption='[[4bld]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='4bld' size='340' side='right'caption='[[4bld]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <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> | + | <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 [https://proteopedia.org/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> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</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> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4bl8|4bl8]], [[4bl9|4bl9]], [[4bla|4bla]], [[4blb|4blb]]</div></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=4bld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bld OCA], [http://pdbe.org/4bld PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bld RCSB], [http://www.ebi.ac.uk/pdbsum/4bld PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bld ProSAT]</span></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=4bld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bld OCA], [https://pdbe.org/4bld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bld RCSB], [https://www.ebi.ac.uk/pdbsum/4bld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bld ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/GLI3_HUMAN 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. | + | [[https://www.uniprot.org/uniprot/GLI3_HUMAN 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 == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI]] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. [[http://www.uniprot.org/uniprot/GLI3_HUMAN 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'.<ref>PMID:10693759</ref> <ref>PMID:11238441</ref> <ref>PMID:17764085</ref> | + | [[https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI]] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. [[https://www.uniprot.org/uniprot/GLI3_HUMAN 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'.<ref>PMID:10693759</ref> <ref>PMID:11238441</ref> <ref>PMID:17764085</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Cherry, A L]] | | [[Category: Cherry, A L]] |
| Structural highlights
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
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