View source for 2e32


==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=''>
== Structural highlights ==
<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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2e32 ProSAT]</span></td></tr>
</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>  [[http://www.uniprot.org/uniprot/SKP1_HUMAN 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.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <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/main_output.php?pdb_ID=2e32 ConSurf].
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== 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<ref>PMID:17389369</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2e32" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Lk3 transgenic mice]]
[[Category: Hasegawa, Y]]
[[Category: Kumanomidou, T]]
[[Category: Mizushima, T]]
[[Category: Tanaka, K]]
[[Category: Yamane, T]]
[[Category: Yoshida, Y]]
[[Category: Fbs1]]
[[Category: Ligase]]
[[Category: Scf]]
[[Category: Ubiquitin]]
[[Category: Ubiquitin ligase]]