| Structural highlights
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] [RAD23_YEAST] Plays a central role both in proteasomal degradation of misfolded proteins and DNA repair. Central component of a complex required to couple deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol. Involved in DNA excision repair. May play a part in DNA damage recognition and/or in altering chromatin structure to allow access by damage-processing enzymes.
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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