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1umh

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'''Structural basis of sugar-recognizing ubiquitin ligase'''<br />
'''Structural basis of sugar-recognizing ubiquitin ligase'''<br />
==Overview==
==Overview==
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SCF(Fbs1) is a ubiquitin ligase that functions in the endoplasmic, reticulum (ER)-associated degradation pathway. Fbs1/Fbx2, a member of the, F-box proteins, recognizes high-mannose oligosaccharides. Efficient, binding to an N-glycan requires di-N-acetylchitobiose (chitobiose). Here, we report the crystal structures of the sugar-binding domain (SBD) of Fbs1, alone and in complex with chitobiose. The SBD is composed of a, ten-stranded antiparallel beta-sandwich. The structure of the, SBD-chitobiose complex includes hydrogen bonds between Fbs1 and chitobiose, and insertion of the methyl group of chitobiose into a small hydrophobic, pocket of Fbs1. Moreover, NMR spectroscopy has demonstrated that the amino, acid residues adjoining the chitobiose-binding site interact with the, outer branches of the carbohydrate moiety. Considering that the innermost, chitobiose moieties in N-glycans are usually involved in intramolecular, interactions with the polypeptide moieties, we propose that Fbs1 interacts, with the chitobiose in unfolded N-glycoprotein, pointing the protein, moiety toward E2 for ubiquitination.
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SCF(Fbs1) is a ubiquitin ligase that functions in the endoplasmic reticulum (ER)-associated degradation pathway. Fbs1/Fbx2, a member of the F-box proteins, recognizes high-mannose oligosaccharides. Efficient binding to an N-glycan requires di-N-acetylchitobiose (chitobiose). Here we report the crystal structures of the sugar-binding domain (SBD) of Fbs1 alone and in complex with chitobiose. The SBD is composed of a ten-stranded antiparallel beta-sandwich. The structure of the SBD-chitobiose complex includes hydrogen bonds between Fbs1 and chitobiose and insertion of the methyl group of chitobiose into a small hydrophobic pocket of Fbs1. Moreover, NMR spectroscopy has demonstrated that the amino acid residues adjoining the chitobiose-binding site interact with the outer branches of the carbohydrate moiety. Considering that the innermost chitobiose moieties in N-glycans are usually involved in intramolecular interactions with the polypeptide moieties, we propose that Fbs1 interacts with the chitobiose in unfolded N-glycoprotein, pointing the protein moiety toward E2 for ubiquitination.
==About this Structure==
==About this Structure==
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1UMH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NI as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UMH OCA].
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1UMH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=NI:'>NI</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UMH OCA].
==Reference==
==Reference==
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[[Category: Iwai, K.]]
[[Category: Iwai, K.]]
[[Category: Kato, K.]]
[[Category: Kato, K.]]
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[[Category: Lee, S.J.]]
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[[Category: Lee, S J.]]
[[Category: Mizushima, T.]]
[[Category: Mizushima, T.]]
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[[Category: RSGI, RIKEN.Structural.Genomics/Proteomics.Initiative.]]
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[[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
[[Category: Tanaka, K.]]
[[Category: Tanaka, K.]]
[[Category: Tsukihara, T.]]
[[Category: Tsukihara, T.]]
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[[Category: ubiquitin ligase]]
[[Category: ubiquitin ligase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 04:14:43 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:26:05 2008''

Revision as of 13:26, 21 February 2008


1umh, resolution 2.00Å

Drag the structure with the mouse to rotate

Structural basis of sugar-recognizing ubiquitin ligase

Overview

SCF(Fbs1) is a ubiquitin ligase that functions in the endoplasmic reticulum (ER)-associated degradation pathway. Fbs1/Fbx2, a member of the F-box proteins, recognizes high-mannose oligosaccharides. Efficient binding to an N-glycan requires di-N-acetylchitobiose (chitobiose). Here we report the crystal structures of the sugar-binding domain (SBD) of Fbs1 alone and in complex with chitobiose. The SBD is composed of a ten-stranded antiparallel beta-sandwich. The structure of the SBD-chitobiose complex includes hydrogen bonds between Fbs1 and chitobiose and insertion of the methyl group of chitobiose into a small hydrophobic pocket of Fbs1. Moreover, NMR spectroscopy has demonstrated that the amino acid residues adjoining the chitobiose-binding site interact with the outer branches of the carbohydrate moiety. Considering that the innermost chitobiose moieties in N-glycans are usually involved in intramolecular interactions with the polypeptide moieties, we propose that Fbs1 interacts with the chitobiose in unfolded N-glycoprotein, pointing the protein moiety toward E2 for ubiquitination.

About this Structure

1UMH is a Single protein structure of sequence from Mus musculus with as ligand. Active as Ubiquitin--protein ligase, with EC number 6.3.2.19 Full crystallographic information is available from OCA.

Reference

Structural basis of sugar-recognizing ubiquitin ligase., Mizushima T, Hirao T, Yoshida Y, Lee SJ, Chiba T, Iwai K, Yamaguchi Y, Kato K, Tsukihara T, Tanaka K, Nat Struct Mol Biol. 2004 Apr;11(4):365-70. Epub 2004 Feb 29. PMID:14990996

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