7CZB

The cryo-EM structure of the ERAD retrotranslocation channel formed by human Derlin-1

Summary for 7CZB

• Entry DOI: 10.2210/pdb7czb/pdb
• EMDB information: 30508
• Descriptor: Derlin-1 (1 entity in total)
• Functional Keywords: endoplasmic reticulum associated degradation, retrotranslocation, cryo-em, transmembrane channels, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 115286.66

Authors

Rao, B.,Li, S.,Yao, D.,Wang, Q.,Xia, Y.,Jia, Y.,Shen, Y.,Cao, Y. (deposition date: 2020-09-07, release date: 2021-03-17, Last modification date: 2024-03-27)

Primary citation

Rao, B.,Li, S.,Yao, D.,Wang, Q.,Xia, Y.,Jia, Y.,Shen, Y.,Cao, Y.
The cryo-EM structure of an ERAD protein channel formed by tetrameric human Derlin-1.
Sci Adv, 7:-, 2021

PubMed Abstract: Endoplasmic reticulum-associated degradation (ERAD) is a process directing misfolded proteins from the ER lumen and membrane to the degradation machinery in the cytosol. A key step in ERAD is the translocation of ER proteins to the cytosol. Derlins are essential for protein translocation in ERAD, but the mechanism remains unclear. Here, we solved the structure of human Derlin-1 by cryo-electron microscopy. The structure shows that Derlin-1 forms a homotetramer that encircles a large tunnel traversing the ER membrane. The tunnel has a diameter of about 12 to 15 angstroms, large enough to allow an α helix to pass through. The structure also shows a lateral gate within the membrane, providing access of transmembrane proteins to the tunnel, and thus, human Derlin-1 forms a protein channel for translocation of misfolded proteins. Our structure is different from the monomeric yeast Derlin structure previously reported, which forms a semichannel with another protein.

PubMed: 33658201
DOI: 10.1126/sciadv.abe8591

Experimental method

ELECTRON MICROSCOPY (3.8 Å)