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| - | [[Image:1x3z.gif|left|200px]] | |
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| - | <!--
| + | ==Structure of a peptide:N-glycanase-Rad23 complex== |
| - | The line below this paragraph, containing "STRUCTURE_1x3z", creates the "Structure Box" on the page.
| + | <StructureSection load='1x3z' size='340' side='right'caption='[[1x3z]], [[Resolution|resolution]] 2.80Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1x3z]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X3Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X3Z FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</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=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PHQ:BENZYL+CHLOROCARBONATE'>PHQ</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | {{STRUCTURE_1x3z| PDB=1x3z | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1x3z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x3z OCA], [https://pdbe.org/1x3z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x3z RCSB], [https://www.ebi.ac.uk/pdbsum/1x3z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x3z ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PNG1_YEAST PNG1_YEAST] 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. Involved in the formation of free oligosaccharide in cytosol.<ref>PMID:10831608</ref> <ref>PMID:12723970</ref> <ref>PMID:12606569</ref> <ref>PMID:14726951</ref> <ref>PMID:15670854</ref> <ref>PMID:16401726</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/x3/1x3z_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1x3z ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | In eukaryotes, misfolded proteins must be distinguished from correctly folded proteins during folding and transport processes by quality control systems. Yeast peptide:N-glycanase (yPNGase) specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists proteasome-mediated glycoprotein degradation by forming a complex with 26S proteasome through DNA repair protein, yRad23. Here, we describe the crystal structures of a yPNGase and XPC-binding domain of yRad23 (yRad23XBD, residues 238-309) complex and of a yPNGase-yRad23XBD complex bound to a caspase inhibitor, Z-VAD-fmk. yPNGase is formed with three domains, a core domain containing a Cys-His-Asp triad, a Zn-binding domain, and a Rad23-binding domain. Both N- and C-terminal helices of yPNGase interact with yRad23 through extensive hydrophobic interactions. The active site of yPNGase is located in a deep cleft that is formed with residues conserved in all PNGase members, and three sugar molecules are bound to this cleft. Complex structures in conjunction with mutational analyses revealed that the walls of the cleft block access to the active site of yPNGase by native glycoprotein, whereas the cleft is sufficiently wide to accommodate denatured glycoprotein, thus explaining the specificity of PNGase for denatured substrates. |
| | | | |
| - | '''Structure of a peptide:N-glycanase-Rad23 complex'''
| + | Structure of a peptide:N-glycanase-Rad23 complex: insight into the deglycosylation for denatured glycoproteins.,Lee JH, Choi JM, Lee C, Yi KJ, Cho Y Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9144-9. Epub 2005 Jun 17. PMID:15964983<ref>PMID:15964983</ref> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | In eukaryotes, misfolded proteins must be distinguished from correctly folded proteins during folding and transport processes by quality control systems. Yeast peptide:N-glycanase (yPNGase) specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists proteasome-mediated glycoprotein degradation by forming a complex with 26S proteasome through DNA repair protein, yRad23. Here, we describe the crystal structures of a yPNGase and XPC-binding domain of yRad23 (yRad23XBD, residues 238-309) complex and of a yPNGase-yRad23XBD complex bound to a caspase inhibitor, Z-VAD-fmk. yPNGase is formed with three domains, a core domain containing a Cys-His-Asp triad, a Zn-binding domain, and a Rad23-binding domain. Both N- and C-terminal helices of yPNGase interact with yRad23 through extensive hydrophobic interactions. The active site of yPNGase is located in a deep cleft that is formed with residues conserved in all PNGase members, and three sugar molecules are bound to this cleft. Complex structures in conjunction with mutational analyses revealed that the walls of the cleft block access to the active site of yPNGase by native glycoprotein, whereas the cleft is sufficiently wide to accommodate denatured glycoprotein, thus explaining the specificity of PNGase for denatured substrates.
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1X3Z is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X3Z OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1x3z" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Structure of a peptide:N-glycanase-Rad23 complex: insight into the deglycosylation for denatured glycoproteins., Lee JH, Choi JM, Lee C, Yi KJ, Cho Y, Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9144-9. Epub 2005 Jun 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15964983 15964983]
| + | *[[Peptide N-glycanase|Peptide N-glycanase]] |
| - | [[Category: Protein complex]] | + | *[[UV excision repair protein 3D structures|UV excision repair protein 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Cho, Y.]] | + | [[Category: Cho Y]] |
| - | [[Category: Choi, J M.]] | + | [[Category: Choi JM]] |
| - | [[Category: Lee, C.]] | + | [[Category: Lee C]] |
| - | [[Category: Lee, J H.]] | + | [[Category: Lee J-H]] |
| - | [[Category: Yi, K J.]] | + | [[Category: Yi KJ]] |
| - | [[Category: Protein-protein-inhibitor complex]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:29:47 2008''
| + | |
| Structural highlights
1x3z is a 3 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.8Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
PNG1_YEAST 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. Involved in the formation of free oligosaccharide in cytosol.[1] [2] [3] [4] [5] [6]
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
In eukaryotes, misfolded proteins must be distinguished from correctly folded proteins during folding and transport processes by quality control systems. Yeast peptide:N-glycanase (yPNGase) specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists proteasome-mediated glycoprotein degradation by forming a complex with 26S proteasome through DNA repair protein, yRad23. Here, we describe the crystal structures of a yPNGase and XPC-binding domain of yRad23 (yRad23XBD, residues 238-309) complex and of a yPNGase-yRad23XBD complex bound to a caspase inhibitor, Z-VAD-fmk. yPNGase is formed with three domains, a core domain containing a Cys-His-Asp triad, a Zn-binding domain, and a Rad23-binding domain. Both N- and C-terminal helices of yPNGase interact with yRad23 through extensive hydrophobic interactions. The active site of yPNGase is located in a deep cleft that is formed with residues conserved in all PNGase members, and three sugar molecules are bound to this cleft. Complex structures in conjunction with mutational analyses revealed that the walls of the cleft block access to the active site of yPNGase by native glycoprotein, whereas the cleft is sufficiently wide to accommodate denatured glycoprotein, thus explaining the specificity of PNGase for denatured substrates.
Structure of a peptide:N-glycanase-Rad23 complex: insight into the deglycosylation for denatured glycoproteins.,Lee JH, Choi JM, Lee C, Yi KJ, Cho Y Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9144-9. Epub 2005 Jun 17. PMID:15964983[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Suzuki T, Park H, Hollingsworth NM, Sternglanz R, Lennarz WJ. PNG1, a yeast gene encoding a highly conserved peptide:N-glycanase. J Cell Biol. 2000 May 29;149(5):1039-52. PMID:10831608
- ↑ Chantret I, Frenoy JP, Moore SE. Free-oligosaccharide control in the yeast Saccharomyces cerevisiae: roles for peptide:N-glycanase (Png1p) and vacuolar mannosidase (Ams1p). Biochem J. 2003 Aug 1;373(Pt 3):901-8. PMID:12723970 doi:http://dx.doi.org/10.1042/BJ20030384
- ↑ Hirsch C, Blom D, Ploegh HL. A role for N-glycanase in the cytosolic turnover of glycoproteins. EMBO J. 2003 Mar 3;22(5):1036-46. PMID:12606569 doi:http://dx.doi.org/10.1093/emboj/cdg107
- ↑ Hirsch C, Misaghi S, Blom D, Pacold ME, Ploegh HL. Yeast N-glycanase distinguishes between native and non-native glycoproteins. EMBO Rep. 2004 Feb;5(2):201-6. Epub 2004 Jan 9. PMID:14726951 doi:http://dx.doi.org/10.1038/sj.embor.7400066
- ↑ Joshi S, Katiyar S, Lennarz WJ. Misfolding of glycoproteins is a prerequisite for peptide: N-glycanase mediated deglycosylation. FEBS Lett. 2005 Jan 31;579(3):823-6. PMID:15670854 doi:http://dx.doi.org/S0014-5793(05)00016-5
- ↑ Kim I, Ahn J, Liu C, Tanabe K, Apodaca J, Suzuki T, Rao H. The Png1-Rad23 complex regulates glycoprotein turnover. J Cell Biol. 2006 Jan 16;172(2):211-9. Epub 2006 Jan 9. PMID:16401726 doi:http://dx.doi.org/jcb.200507149
- ↑ Lee JH, Choi JM, Lee C, Yi KJ, Cho Y. Structure of a peptide:N-glycanase-Rad23 complex: insight into the deglycosylation for denatured glycoproteins. Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9144-9. Epub 2005 Jun 17. PMID:15964983
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