8ZPW

Cryo-EM structure of the yeast Htm1/Pdi1 complex at a resolution of 3.0 angstrom

Summary for 8ZPW

• Entry DOI: 10.2210/pdb8zpw/pdb
• EMDB information: 60365
• Descriptor: ER degradation-enhancing alpha-mannosidase-like protein 1, Protein disulfide-isomerase, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: complex, carbohydrate cleavage, peptide binding, peptide binding protein
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 150320.03

Authors

Wu, X.W.,Zhao, D.,Rapoport, T.A. (deposition date: 2024-05-31, release date: 2024-11-13)

Primary citation

Zhao, D.,Wu, X.,Rapoport, T.A.
Initiation of ERAD by the bifunctional complex of Mnl1 mannosidase and protein disulfide isomerase.
Biorxiv, 2024

PubMed Abstract: Misfolded glycoproteins in the endoplasmic reticulum (ER) lumen are translocated into the cytosol and degraded by the proteasome, a conserved process called ER-associated protein degradation (ERAD). In , the glycan of these proteins is trimmed by the luminal mannosidase Mnl1 (Htm1) to generate a signal that triggers degradation. Curiously, Mnl1 is permanently associated with protein disulfide isomerase (Pdi1). Here, we have used cryo-electron microscopy, biochemical, and experiments to clarify how this complex initiates ERAD. The Mnl1-Pdi1 complex first de-mannosylates misfolded, globular proteins that are recognized through a C-terminal domain (CTD) of Mnl1; Pdi1 causes the CTD to ignore completely unfolded polypeptides. The disulfides of these globular proteins are then reduced by the Pdi1 component of the complex, generating unfolded polypeptides that can be translocated across the membrane. Mnl1 blocks the canonical oxidative function of Pdi1, but allows it to function as the elusive disulfide reductase in ERAD.

PubMed: 39464000
DOI: 10.1101/2024.10.17.618908

Experimental method

ELECTRON MICROSCOPY (3 Å)