4M8G: Crystal Structure Of Se-met Hn33/tusc3

Citation:
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.
PDB ID: 4M8GDownload
MMDB ID: 118602
PDB Deposition Date: 2013/8/13
Updated in MMDB: 2014/05
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 4M8G: monomeric; determined by author and by software (PISA)
Molecular Components in 4M8G
Label Count Molecule
Protein (1 molecule)
1
Tumor Suppressor Candidate 3(Gene symbol: TUSC3)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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