4m92: Difference between revisions

Latest revision as of 16:34, 20 September 2023

Crystal structure of hN33/Tusc3-peptide 2

Structural highlights

4m92 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.6Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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:https://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:https://dx.doi.org/10.1016/j.str.2014.02.013

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OCA

[1] 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:https://dx.doi.org/0908332106

[2] 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:https://dx.doi.org/10.1016/j.str.2014.02.013

[1]

[2]

@@ Line 1: / Line 1: @@
-{{STRUCTURE_4m92|  PDB=4m92  |  SCENE=  }}
-===Crystal structure of hN33/Tusc3-peptide 2===
-==Disease==
+==Crystal structure of hN33/Tusc3-peptide 2==
-[[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/IRPL1_HUMAN IRPL1_HUMAN]] Defects in IL1RAPL1 are the cause of mental retardation X-linked type 21 (MRX21) [MIM:[http://omim.org/entry/300143 300143]]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs.<ref>PMID:10757639</ref> <ref>PMID:16470793</ref>
+<StructureSection load='4m92' size='340' side='right'caption='[[4m92]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4m92]] 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=4M92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M92 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</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=4m92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m92 OCA], [https://pdbe.org/4m92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m92 RCSB], [https://www.ebi.ac.uk/pdbsum/4m92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m92 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[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 ==
+[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;">
+== 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.
-==Function==
+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<ref>PMID:24685145</ref>
-[[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/IRPL1_HUMAN IRPL1_HUMAN]] May regulate secretion and presynaptic differentiation through inhibition of the activity of N-type voltage-gated calcium channel. May activate the MAP kinase JNK. Plays a role in presynaptic and postsynaptic differentiation and dendritic spine formation in neurons.<ref>PMID:12783849</ref> <ref>PMID:15123616</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4m92]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M92 OCA].
+</div>
+<div class="pdbe-citations 4m92" style="background-color:#fffaf0;"></div>
-==Reference==
+== References ==
-<references group="xtra"/><references/>
+<references/>
-[[Category: Aebi, M.]]
+__TOC__
-[[Category: Brozzo, M S.]]
+</StructureSection>
-[[Category: Glockshuber, R.]]
+[[Category: Homo sapiens]]
-[[Category: Malojcic, G.]]
+[[Category: Large Structures]]
-[[Category: Mohorko, E.]]
+[[Category: Aebi M]]
-[[Category: Owen, R L.]]
+[[Category: Brozzo MS]]
-[[Category: Oxidoreductase]]
+[[Category: Glockshuber R]]
-[[Category: Redox-active protein]]
+[[Category: Malojcic G]]
-[[Category: Thiol/disulfide exchange reaction]]
+[[Category: Mohorko E]]
-[[Category: Thiol/disulfide oxidoreductase]]
+[[Category: Owen RL]]
-[[Category: Thioredoxin-like fold]]

4m92: Difference between revisions

Latest revision as of 16:34, 20 September 2023

Crystal structure of hN33/Tusc3-peptide 2

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

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