3.A.16.1.1
Mammalian ER retrotranslocon. The Grp170 protein plays a role during ERAD, positioning this client-release factor at the retrotranslocation site, allowing a mechanism to couple client release from BiP and retrotranslocation (Inoue and Tsai, 2016). The cryo-EM structure of the ERAD protein channel, formed by tetrameric human Derlin-1, has been solved (Rao et al. 2021).  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 shows a lateral gate within the membrane, providing access of transmembrane proteins to the tunnel. Thus, Derlin-1 forms a protein channel for translocation of misfolded proteins. This structure is different from the monomeric yeast Derlin structure previously reported, which forms a semichannel with another protein (Rao et al. 2021).