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| | <StructureSection load='1umh' size='340' side='right'caption='[[1umh]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='1umh' size='340' side='right'caption='[[1umh]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1umh]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UMH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1UMH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1umh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UMH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UMH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1umi|1umi]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mouse ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=1umh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1umh OCA], [https://pdbe.org/1umh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1umh RCSB], [https://www.ebi.ac.uk/pdbsum/1umh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1umh ProSAT], [https://www.topsan.org/Proteins/RSGI/1umh TOPSAN]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1umh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1umh OCA], [http://pdbe.org/1umh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1umh RCSB], [http://www.ebi.ac.uk/pdbsum/1umh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1umh ProSAT], [http://www.topsan.org/Proteins/RSGI/1umh TOPSAN]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FBX2_MOUSE FBX2_MOUSE]] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Involved in the endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins by recognizing and binding sugar chains on unfolded glycoproteins that are retrotranslocated into the cytosol and promoting their ubiquitination and subsequent degradation. Prevents formation of cytosolic aggregates of unfolded glycoproteins that have been retrotranslocated into the cytosol. Able to recognize and bind denatured glycoproteins, preferentially those of the high-mannose type.<ref>PMID:12140560</ref> <ref>PMID:15723043</ref> <ref>PMID:17720138</ref> <ref>PMID:17215248</ref> <ref>PMID:14990996</ref> | + | [https://www.uniprot.org/uniprot/FBX2_MOUSE FBX2_MOUSE] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Involved in the endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins by recognizing and binding sugar chains on unfolded glycoproteins that are retrotranslocated into the cytosol and promoting their ubiquitination and subsequent degradation. Prevents formation of cytosolic aggregates of unfolded glycoproteins that have been retrotranslocated into the cytosol. Able to recognize and bind denatured glycoproteins, preferentially those of the high-mannose type.<ref>PMID:12140560</ref> <ref>PMID:15723043</ref> <ref>PMID:17720138</ref> <ref>PMID:17215248</ref> <ref>PMID:14990996</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ubiquitin--protein ligase]]
| + | [[Category: Chiba T]] |
| - | [[Category: Chiba, T]] | + | [[Category: Hirao T]] |
| - | [[Category: Hirao, T]] | + | [[Category: Iwai K]] |
| - | [[Category: Iwai, K]] | + | [[Category: Kato K]] |
| - | [[Category: Kato, K]] | + | [[Category: Lee SJ]] |
| - | [[Category: Lee, S J]] | + | [[Category: Mizushima T]] |
| - | [[Category: Mizushima, T]] | + | [[Category: Tanaka K]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Tsukihara T]] |
| - | [[Category: Tanaka, K]] | + | [[Category: Yamaguchi Y]] |
| - | [[Category: Tsukihara, T]] | + | [[Category: Yoshida Y]] |
| - | [[Category: Yamaguchi, Y]] | + | |
| - | [[Category: Yoshida, Y]] | + | |
| - | [[Category: Lectin]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Rsgi]]
| + | |
| - | [[Category: Scf]]
| + | |
| - | [[Category: Ubiquitin]]
| + | |
| - | [[Category: Ubiquitin ligase]]
| + | |
| Structural highlights
Function
FBX2_MOUSE Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Involved in the endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins by recognizing and binding sugar chains on unfolded glycoproteins that are retrotranslocated into the cytosol and promoting their ubiquitination and subsequent degradation. Prevents formation of cytosolic aggregates of unfolded glycoproteins that have been retrotranslocated into the cytosol. Able to recognize and bind denatured glycoproteins, preferentially those of the high-mannose type.[1] [2] [3] [4] [5]
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
SCF(Fbs1) is a ubiquitin ligase that functions in the endoplasmic reticulum (ER)-associated degradation pathway. Fbs1/Fbx2, a member of the F-box proteins, recognizes high-mannose oligosaccharides. Efficient binding to an N-glycan requires di-N-acetylchitobiose (chitobiose). Here we report the crystal structures of the sugar-binding domain (SBD) of Fbs1 alone and in complex with chitobiose. The SBD is composed of a ten-stranded antiparallel beta-sandwich. The structure of the SBD-chitobiose complex includes hydrogen bonds between Fbs1 and chitobiose and insertion of the methyl group of chitobiose into a small hydrophobic pocket of Fbs1. Moreover, NMR spectroscopy has demonstrated that the amino acid residues adjoining the chitobiose-binding site interact with the outer branches of the carbohydrate moiety. Considering that the innermost chitobiose moieties in N-glycans are usually involved in intramolecular interactions with the polypeptide moieties, we propose that Fbs1 interacts with the chitobiose in unfolded N-glycoprotein, pointing the protein moiety toward E2 for ubiquitination.
Structural basis of sugar-recognizing ubiquitin ligase.,Mizushima T, Hirao T, Yoshida Y, Lee SJ, Chiba T, Iwai K, Yamaguchi Y, Kato K, Tsukihara T, Tanaka K Nat Struct Mol Biol. 2004 Apr;11(4):365-70. Epub 2004 Feb 29. PMID:14990996[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yoshida Y, Chiba T, Tokunaga F, Kawasaki H, Iwai K, Suzuki T, Ito Y, Matsuoka K, Yoshida M, Tanaka K, Tai T. E3 ubiquitin ligase that recognizes sugar chains. Nature. 2002 Jul 25;418(6896):438-42. PMID:12140560 doi:10.1038/nature00890
- ↑ Yoshida Y, Adachi E, Fukiya K, Iwai K, Tanaka K. Glycoprotein-specific ubiquitin ligases recognize N-glycans in unfolded substrates. EMBO Rep. 2005 Mar;6(3):239-44. PMID:15723043 doi:http://dx.doi.org/10.1038/sj.embor.7400351
- ↑ Yamaguchi Y, Hirao T, Sakata E, Kamiya Y, Kurimoto E, Yoshida Y, Suzuki T, Tanaka K, Kato K. Fbs1 protects the malfolded glycoproteins from the attack of peptide:N-glycanase. Biochem Biophys Res Commun. 2007 Oct 26;362(3):712-6. Epub 2007 Aug 20. PMID:17720138 doi:http://dx.doi.org/10.1016/j.bbrc.2007.08.056
- ↑ Yoshida Y, Murakami A, Iwai K, Tanaka K. A neural-specific F-box protein Fbs1 functions as a chaperone suppressing glycoprotein aggregation. J Biol Chem. 2007 Mar 9;282(10):7137-44. Epub 2007 Jan 10. PMID:17215248 doi:http://dx.doi.org/10.1074/jbc.M611168200
- ↑ Mizushima T, Hirao T, Yoshida Y, Lee SJ, Chiba T, Iwai K, Yamaguchi Y, Kato K, Tsukihara T, Tanaka K. Structural basis of sugar-recognizing ubiquitin ligase. Nat Struct Mol Biol. 2004 Apr;11(4):365-70. Epub 2004 Feb 29. PMID:14990996 doi:http://dx.doi.org/10.1038/nsmb732
- ↑ Mizushima T, Hirao T, Yoshida Y, Lee SJ, Chiba T, Iwai K, Yamaguchi Y, Kato K, Tsukihara T, Tanaka K. Structural basis of sugar-recognizing ubiquitin ligase. Nat Struct Mol Biol. 2004 Apr;11(4):365-70. Epub 2004 Feb 29. PMID:14990996 doi:http://dx.doi.org/10.1038/nsmb732
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