4M8G

Crystal structure of Se-Met hN33/Tusc3

Summary for 4M8G

• Entry DOI: 10.2210/pdb4m8g/pdb
• Related: 4M90 4M91 4M92
• Descriptor: Tumor suppressor candidate 3 (2 entities in total)
• Functional Keywords: thioredoxin-like fold; thiol/disulfide oxidoreductase, thiol/disulfide exchange reactions, redox-active protein, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity): Q13454
• Total number of polymer chains: 2
• Total formula weight: 38940.27

Authors

Mohorko, E.,Owen, R.L.,Malojcic, G.,Brozzo, M.S.,Aebi, M.,Glockshuber, R. (deposition date: 2013-08-13, release date: 2014-03-26, Last modification date: 2024-11-20)

Primary citation

Mohorko, E.,Owen, R.L.,Malojcic, G.,Brozzo, M.S.,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, 22:590-601, 2014

PubMed Abstract: 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.

PubMed: 24685145
DOI: 10.1016/j.str.2014.02.013

Experimental method

X-RAY DIFFRACTION (2 Å)