2f4m
From Proteopedia
(New page: 200px<br /><applet load="2f4m" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f4m, resolution 1.85Å" /> '''The Mouse PNGase-HR2...) |
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| - | [[Image:2f4m.gif|left|200px]]<br /><applet load="2f4m" size=" | + | [[Image:2f4m.gif|left|200px]]<br /><applet load="2f4m" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2f4m, resolution 1.85Å" /> | caption="2f4m, resolution 1.85Å" /> | ||
'''The Mouse PNGase-HR23 Complex Reveals a Complete Remodulation of the Protein-Protein Interface Compared to its Yeast Orthologs'''<br /> | '''The Mouse PNGase-HR23 Complex Reveals a Complete Remodulation of the Protein-Protein Interface Compared to its Yeast Orthologs'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Peptide N-glycanase removes N-linked oligosaccharides from misfolded | + | 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== | ==About this Structure== | ||
| - | 2F4M 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:// | + | 2F4M 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 <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=CL:'>CL</scene> 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://oca.weizmann.ac.il/oca-bin/ocashort?id=2F4M OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Kisker, C.]] | [[Category: Kisker, C.]] | ||
| - | [[Category: Lennarz, W | + | [[Category: Lennarz, W J.]] |
[[Category: Schindelin, H.]] | [[Category: Schindelin, H.]] | ||
[[Category: Wang, L.]] | [[Category: Wang, L.]] | ||
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[[Category: ubiquitin-dependent protein degradation]] | [[Category: ubiquitin-dependent protein degradation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:17:39 2008'' |
Revision as of 15:17, 21 February 2008
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The Mouse PNGase-HR23 Complex Reveals a Complete Remodulation of the Protein-Protein Interface Compared to its Yeast Orthologs
Overview
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
2F4M is a Protein complex structure of sequences from Mus musculus with and as ligands. Active as Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase, with EC number 3.5.1.52 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 17:17:39 2008
Categories: Mus musculus | Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase | Protein complex | Kisker, C. | Lennarz, W J. | Schindelin, H. | Wang, L. | Zhao, G. | Zhou, X. | CL | ZN | Glycoproteins | Nucleotide excision repair | Peptide:n-glycanase | Transglutaminase | Ubiquitin-dependent protein degradation
