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2e32

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Revision as of 06:54, 6 June 2018

Structural basis for selection of glycosylated substrate by SCFFbs1 ubiquitin ligase

Structural highlights

2e32 is a 4 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2e31, 2e33
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [SKP1_HUMAN] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.^[6] ^[7]

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

The ubiquitin ligase complex SCF(Fbs1), which contributes to the ubiquitination of glycoproteins, is involved in the endoplasmic reticulum-associated degradation pathway. In SCF ubiquitin ligases, a diverse array of F-box proteins confers substrate specificity. Fbs1/Fbx2, a member of the F-box protein family, recognizes high-mannose oligosaccharides. To elucidate the structural basis of SCF(Fbs1) function, we determined the crystal structures of the Skp1-Fbs1 complex and the sugar-binding domain (SBD) of the Fbs1-glycoprotein complex. The mechanistic model indicated by the structures appears to be well conserved among the SCF ubiquitin ligases. The structure of the SBD-glycoprotein complex indicates that the SBD primarily recognizes Man(3)GlcNAc(2), thereby explaining the broad activity of the enzyme against various glycoproteins. Comparison of two crystal structures of the Skp1-Fbs1 complex revealed the relative motion of a linker segment between the F-box and the SBD domains, which might underlie the ability of the complex to recognize different acceptor lysine residues for ubiquitination.

Structural basis for the selection of glycosylated substrates by SCF(Fbs1) ubiquitin ligase.,Mizushima T, Yoshida Y, Kumanomidou T, Hasegawa Y, Suzuki A, Yamane T, Tanaka K Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5777-81. Epub 2007 Mar 26. PMID:17389369^[8]

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
↑ Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP. Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase. Mol Cell. 2005 Oct 7;20(1):9-19. PMID:16209941 doi:10.1016/j.molcel.2005.09.003
↑ Li Y, Hao B. Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase. J Biol Chem. 2010 Apr 30;285(18):13896-906. Epub 2010 Feb 24. PMID:20181953 doi:10.1074/jbc.M110.111518
↑ Mizushima T, Yoshida Y, Kumanomidou T, Hasegawa Y, Suzuki A, Yamane T, Tanaka K. Structural basis for the selection of glycosylated substrates by SCF(Fbs1) ubiquitin ligase. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5777-81. Epub 2007 Mar 26. PMID:17389369

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/2e32"

@@ Line 1: / Line 1: @@
 ==Structural basis for selection of glycosylated substrate by SCFFbs1 ubiquitin ligase==
 <StructureSection load='2e32' size='340' side='right' caption='[[2e32]], [[Resolution|resolution]] 3.52&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2e32]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [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=2E32 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2E32 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2e31|2e31]], [[2e33|2e33]]</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=2e32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e32 OCA], [http://pdbe.org/2e32 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2e32 RCSB], [http://www.ebi.ac.uk/pdbsum/2e32 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=2e32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e32 OCA], [http://pdbe.org/2e32 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2e32 RCSB], [http://www.ebi.ac.uk/pdbsum/2e32 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2e32 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 12: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e3/2e32_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e3/2e32_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2e32 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

2e32

From Proteopedia

Revision as of 06:54, 6 June 2018

Structural basis for selection of glycosylated substrate by SCFFbs1 ubiquitin ligase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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