2rj2

From Proteopedia

(Difference between revisions)

Revision as of 19:41, 24 December 2014

Crystal Structure of the Sugar Recognizing SCF Ubiquitin Ligase at 1.7 Resolution

Structural highlights

2rj2 is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1umh, 1umi
Gene:	Fbxo2, Fbx2 (Mus musculus)
Activity:	Ubiquitin--protein ligase, with EC number 6.3.2.19
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/2rj2"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2rj2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2RJ2 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1umh|1umh]], [[1umi|1umi]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1umh|1umh]], [[1umi|1umi]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fbxo2, Fbx2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fbxo2, Fbx2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
-<tr><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='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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rj2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rj2 RCSB], [http://www.ebi.ac.uk/pdbsum/2rj2 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=2rj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rj2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rj2 RCSB], [http://www.ebi.ac.uk/pdbsum/2rj2 PDBsum]</span></td></tr>
-<table>
+</table>
+== 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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 35: @@
 [[Category: Mus musculus]]
 [[Category: Ubiquitin--protein ligase]]
-[[Category: Mizushima, T.]]
+[[Category: Mizushima, T]]
-[[Category: Tanaka, K.]]
+[[Category: Tanaka, K]]
-[[Category: Vaijayanthimala, S.]]
+[[Category: Vaijayanthimala, S]]
-[[Category: Velmurugan, D.]]
+[[Category: Velmurugan, D]]
-[[Category: Yamane, T.]]
+[[Category: Yamane, T]]
-[[Category: Yoshida, Y.]]
+[[Category: Yoshida, Y]]
 [[Category: Lectin]]
 [[Category: Ligase]]

2rj2

From Proteopedia

Revision as of 19:41, 24 December 2014

Crystal Structure of the Sugar Recognizing SCF Ubiquitin Ligase at 1.7 Resolution

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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