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| | ==crystal structure of hN33/Tusc3-peptide 1== | | ==crystal structure of hN33/Tusc3-peptide 1== |
| - | <StructureSection load='4m91' size='340' side='right' caption='[[4m91]], [[Resolution|resolution]] 1.10Å' scene=''> | + | <StructureSection load='4m91' size='340' side='right'caption='[[4m91]], [[Resolution|resolution]] 1.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4m91]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M91 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M91 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4m91]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M91 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M91 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m8g|4m8g]], [[4m90|4m90]], [[4m92|4m92]]</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4m91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m91 OCA], [https://pdbe.org/4m91 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m91 RCSB], [https://www.ebi.ac.uk/pdbsum/4m91 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m91 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TUSC3, N33 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CRBN, AD-006 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <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=4m91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m91 OCA], [http://pdbe.org/4m91 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m91 RCSB], [http://www.ebi.ac.uk/pdbsum/4m91 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m91 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TUSC3_HUMAN TUSC3_HUMAN]] Autosomal recessive nonsyndromic intellectual deficit. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/CRBN_HUMAN CRBN_HUMAN]] Autosomal recessive nonsyndromic intellectual deficit;Distal monosomy 3p. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/TUSC3_HUMAN TUSC3_HUMAN] Autosomal recessive nonsyndromic intellectual deficit. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TUSC3_HUMAN TUSC3_HUMAN]] Magnesium transporter. May be involved in N-glycosylation through its association with N-oligosaccharyl transferase.<ref>PMID:19717468</ref> [[http://www.uniprot.org/uniprot/CRBN_HUMAN CRBN_HUMAN]] Component of some DCX (DDB1-CUL4-X-box) E3 protein ligase complex, a complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins and is required for limb outgrowth and expression of the fibroblast growth factor FGF8. In the complex, may act as a substrate receptor. Regulates the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1.<ref>PMID:18414909</ref> <ref>PMID:20223979</ref> | + | [https://www.uniprot.org/uniprot/TUSC3_HUMAN TUSC3_HUMAN] Magnesium transporter. May be involved in N-glycosylation through its association with N-oligosaccharyl transferase.<ref>PMID:19717468</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Aebi, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Brozzo, M S]] | + | [[Category: Aebi M]] |
| - | [[Category: Glockshuber, R]] | + | [[Category: Brozzo MS]] |
| - | [[Category: Malojcic, G]] | + | [[Category: Glockshuber R]] |
| - | [[Category: Mohorko, E]] | + | [[Category: Malojcic G]] |
| - | [[Category: Owen, R L]] | + | [[Category: Mohorko E]] |
| - | [[Category: Endoplasmic reticulum]]
| + | [[Category: Owen RL]] |
| - | [[Category: Formation of mixed disulfide]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Thioredoxin-like fold]]
| + | |
| Structural highlights
Disease
TUSC3_HUMAN Autosomal recessive nonsyndromic intellectual deficit. The disease is caused by mutations affecting the gene represented in this entry.
Function
TUSC3_HUMAN Magnesium transporter. May be involved in N-glycosylation through its association with N-oligosaccharyl transferase.[1]
Publication Abstract from PubMed
N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential in eukaryotes and catalyzed by oligosaccharyl transferase (OST). Human OST is a hetero-oligomer of seven subunits. The subunit N33/Tusc3 is a tumor suppressor candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic mental retardation. Here, we show that N33/Tusc3 possesses a membrane-anchored N-terminal thioredoxin domain located in the ER lumen that may form transient mixed disulfide complexes with OST substrates. X-ray structures of complexes between N33/Tusc3 and two different peptides as model substrates reveal a defined peptide-binding groove adjacent to the active site that can accommodate peptides in opposite orientations. Structural and biochemical data show that N33/Tusc3 prefers peptides bearing a hydrophobic residue two residues away from the cysteine forming the mixed disulfide with N33/Tusc3. Our results support a model in which N33/Tusc3 increases glycosylation efficiency for a subset of human glycoproteins by slowing glycoprotein folding.
Structural basis of substrate specificity of human oligosaccharyl transferase subunit n33/tusc3 and its role in regulating protein N-glycosylation.,Mohorko E, Owen RL, Malojcic G, Brozzo MS, Aebi M, Glockshuber R Structure. 2014 Apr 8;22(4):590-601. doi: 10.1016/j.str.2014.02.013. Epub 2014, Mar 27. PMID:24685145[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhou H, Clapham DE. Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15750-5. Epub 2009 Aug 26. PMID:19717468 doi:http://dx.doi.org/0908332106
- ↑ Mohorko E, Owen RL, Malojcic G, Brozzo MS, Aebi M, Glockshuber R. Structural basis of substrate specificity of human oligosaccharyl transferase subunit n33/tusc3 and its role in regulating protein N-glycosylation. Structure. 2014 Apr 8;22(4):590-601. doi: 10.1016/j.str.2014.02.013. Epub 2014, Mar 27. PMID:24685145 doi:http://dx.doi.org/10.1016/j.str.2014.02.013
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