2f4o: Difference between revisions

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-[[Image:2f4o.gif|left|200px]]<br /><applet load="2f4o" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2f4o, resolution 2.26&Aring;" />
-'''The Mouse PNGase-HR23 Complex Reveals a Complete Remodulation of the Protein-Protein Interface Compared to its Yeast Orthologs'''<br />
-==Overview==
+==The Mouse PNGase-HR23 Complex Reveals a Complete Remodulation of the Protein-Protein Interface Compared to its Yeast Orthologs==
-Peptide N-glycanase removes N-linked oligosaccharides from misfolded, glycoproteins as part of the endoplasmic reticulum-associated degradation, pathway. This process involves the formation of a tight complex of peptide, N-glycanase with Rad23 in yeast and the orthologous HR23 proteins in, mammals. In addition to its function in endoplasmic reticulum-associated, degradation, HR23 is also involved in DNA repair, where it plays an, important role in damage recognition in complex with the xeroderma, pigmentosum group C protein. To characterize the dual role of HR23, we, have determined the high resolution crystal structure of the mouse peptide, N-glycanase catalytic core in complex with the xeroderma pigmentosum group, C binding domain from HR23B. Peptide N-glycanase features a large cleft, between its catalytic cysteine protease core and zinc binding domain., Opposite the zinc binding domain is the HR23B-interacting region, and, surprisingly, the complex interface is fundamentally different from the, orthologous yeast peptide N-glycanase-Rad23 complex. Different regions on, both proteins are involved in complex formation, revealing an amazing, degree of divergence in the interaction between two highly homologous, proteins. Furthermore, the mouse peptide N-glycanase-HR23B complex mimics, the interaction between xeroderma pigmentosum group C and HR23B, thereby, providing a first structural model of how the two proteins interact within, the nucleotide excision repair cascade in higher eukaryotes. The different, interaction interfaces of the xeroderma pigmentosum group C binding, domains in yeast and mammals suggest a co-evolution of the endoplasmic, reticulum-associated degradation and DNA repair pathways.
+<StructureSection load='2f4o' size='340' side='right'caption='[[2f4o]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2f4o]] is a 3 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=2F4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F4O FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.26&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CF0:FLUOROMETHANE'>CF0</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PHQ:BENZYL+CHLOROCARBONATE'>PHQ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2f4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f4o OCA], [https://pdbe.org/2f4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f4o RCSB], [https://www.ebi.ac.uk/pdbsum/2f4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f4o ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NGLY1_MOUSE NGLY1_MOUSE] Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins.<ref>PMID:11562482</ref> <ref>PMID:12606569</ref> <ref>PMID:15358861</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/f4/2f4o_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=2f4o ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Peptide N-glycanase removes N-linked oligosaccharides from misfolded glycoproteins as part of the endoplasmic reticulum-associated degradation pathway. This process involves the formation of a tight complex of peptide N-glycanase with Rad23 in yeast and the orthologous HR23 proteins in mammals. In addition to its function in endoplasmic reticulum-associated degradation, HR23 is also involved in DNA repair, where it plays an important role in damage recognition in complex with the xeroderma pigmentosum group C protein. To characterize the dual role of HR23, we have determined the high resolution crystal structure of the mouse peptide N-glycanase catalytic core in complex with the xeroderma pigmentosum group C binding domain from HR23B. Peptide N-glycanase features a large cleft between its catalytic cysteine protease core and zinc binding domain. Opposite the zinc binding domain is the HR23B-interacting region, and surprisingly, the complex interface is fundamentally different from the orthologous yeast peptide N-glycanase-Rad23 complex. Different regions on both proteins are involved in complex formation, revealing an amazing degree of divergence in the interaction between two highly homologous proteins. Furthermore, the mouse peptide N-glycanase-HR23B complex mimics the interaction between xeroderma pigmentosum group C and HR23B, thereby providing a first structural model of how the two proteins interact within the nucleotide excision repair cascade in higher eukaryotes. The different interaction interfaces of the xeroderma pigmentosum group C binding domains in yeast and mammals suggest a co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways.
-==About this Structure==
+Structure of the mouse peptide N-glycanase-HR23 complex suggests co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways.,Zhao G, Zhou X, Wang L, Li G, Kisker C, Lennarz WJ, Schindelin H J Biol Chem. 2006 May 12;281(19):13751-61. Epub 2006 Feb 24. PMID:16500903<ref>PMID:16500903</ref>
-F4O is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine_amidase Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.52 3.5.1.52] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2F4O OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Structure of the mouse peptide N-glycanase-HR23 complex suggests co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways., Zhao G, Zhou X, Wang L, Li G, Kisker C, Lennarz WJ, Schindelin H, J Biol Chem. 2006 May 12;281(19):13751-61. Epub 2006 Feb 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16500903 16500903]
+</div>
+<div class="pdbe-citations 2f4o" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Peptide N-glycanase|Peptide N-glycanase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase]]
+[[Category: Kisker C]]
-[[Category: Protein complex]]
+[[Category: Lennarz WJ]]
-[[Category: Kisker, C.]]
+[[Category: Schindelin H]]
-[[Category: Lennarz, W.J.]]
+[[Category: Wang L]]
-[[Category: Schindelin, H.]]
+[[Category: Zhao G]]
-[[Category: Wang, L.]]
+[[Category: Zhou X]]
-[[Category: Zhao, G.]]
-[[Category: Zhou, X.]]
-[[Category: CL]]
-[[Category: ZN]]
-[[Category: glycoproteins]]
-[[Category: nucleotide excision repair]]
-[[Category: peptide:n-glycanase]]
-[[Category: transglutaminase]]
-[[Category: ubiquitin-dependent protein degradation]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:21:54 2007''