2f4o: Difference between revisions

Revision as of 18:17, 21 February 2008

The Mouse PNGase-HR23 Complex Reveals a Complete Remodulation of the Protein-Protein Interface Compared to its Yeast Orthologs

OverviewOverview

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 StructureAbout this Structure

2F4O 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.

ReferenceReference

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

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OCA

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-[[Image:2f4o.gif|left|200px]]<br /><applet load="2f4o" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2f4o.gif|left|200px]]<br /><applet load="2f4o" size="350" 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==
-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.
+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==
-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].
+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 <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=2F4O OCA].
 ==Reference==
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 [[Category: Protein complex]]
 [[Category: Kisker, C.]]
-[[Category: Lennarz, W.J.]]
+[[Category: Lennarz, W J.]]
 [[Category: Schindelin, H.]]
 [[Category: Wang, L.]]
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 [[Category: ubiquitin-dependent protein degradation]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:21:54 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:17:39 2008''