[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
