2hpj

From Proteopedia

(Difference between revisions)

Revision as of 07:27, 10 September 2015

Crystal structure of the PUB domain of mouse PNGase

Structural highlights

2hpj is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2hpl
Gene:	Ngly1 (LK3 transgenic mice)
Activity:	Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase, with EC number 3.5.1.52
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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.^[1] ^[2] ^[3]

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

During endoplasmic reticulum-associated degradation, the multifunctional AAA ATPase p97 is part of a protein degradation complex. p97 associates via its N-terminal domain with various cofactors to recruit ubiquitinated substrates. It also interacts with alternative substrate-processing cofactors, such as Ufd2, Ufd3, and peptide:N-glycanase (PNGase) in higher eukaryotes. These cofactors determine different fates of the substrates and they all bind outside of the N-terminal domain of p97. Here, we describe a cofactor-binding motif of p97 contained within the last 10 amino acid residues of the C terminus, which is both necessary and sufficient to mediate interactions of p97 with PNGase and Ufd3. The crystal structure of the N-terminal domain of PNGase in complex with this motif provides detailed insight into the interaction between p97 and its substrate-processing cofactors. Phosphorylation of p97's highly conserved penultimate tyrosine residue, which is the main phosphorylation site during T cell receptor stimulation, completely blocks binding of either PNGase or Ufd3 to p97. This observation suggests that phosphorylation of this residue modulates endoplasmic reticulum-associated protein degradation activity by discharging substrate-processing cofactors.

Studies on peptide:N-glycanase-p97 interaction suggest that p97 phosphorylation modulates endoplasmic reticulum-associated degradation.,Zhao G, Zhou X, Wang L, Li G, Schindelin H, Lennarz WJ Proc Natl Acad Sci U S A. 2007 May 22;104(21):8785-90. Epub 2007 May 11. PMID:17496150^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Park H, Suzuki T, Lennarz WJ. Identification of proteins that interact with mammalian peptide:N-glycanase and implicate this hydrolase in the proteasome-dependent pathway for protein degradation. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11163-8. Epub 2001 Sep 18. PMID:11562482 doi:http://dx.doi.org/10.1073/pnas.201393498
↑ 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
↑ Katiyar S, Li G, Lennarz WJ. A complex between peptide:N-glycanase and two proteasome-linked proteins suggests a mechanism for the degradation of misfolded glycoproteins. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13774-9. Epub 2004 Sep 9. PMID:15358861 doi:http://dx.doi.org/10.1073/pnas.0405663101
↑ Zhao G, Zhou X, Wang L, Li G, Schindelin H, Lennarz WJ. Studies on peptide:N-glycanase-p97 interaction suggest that p97 phosphorylation modulates endoplasmic reticulum-associated degradation. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8785-90. Epub 2007 May 11. PMID:17496150

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2hpj"

@@ Line 2: / Line 2: @@
 <StructureSection load='2hpj' size='340' side='right' caption='[[2hpj]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2hpj]] 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=2HPJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HPJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2hpj]] is a 1 chain structure with sequence from [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=2HPJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HPJ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hpl|2hpl]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ngly1 ([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">Ngly1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </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=2hpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hpj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hpj RCSB], [http://www.ebi.ac.uk/pdbsum/2hpj 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=2hpj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hpj OCA], [http://pdbe.org/2hpj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hpj RCSB], [http://www.ebi.ac.uk/pdbsum/2hpj PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://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]]
@@ Line 27: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2hpj" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 34: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Mus musculus]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Lennarz, W]]
 [[Category: Li, G]]

2hpj

From Proteopedia

Revision as of 07:27, 10 September 2015

Crystal structure of the PUB domain of mouse PNGase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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