Guardians of the ERAD Galaxy Zhihao Sun, Jeffrey L. Brodsky  Cell  Volume 171, Issue 2, Pages 267-268 (October 2017) DOI: 10.1016/j.cell.2017.09.023 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 The S-E Complex and N-Linked Glycans Facilitate ER Quality Control Nascent polypeptides in the ER lumen either fold and exit the ER (right) or are targeted for ERAD (left). The SUN domain (pictured) in the S-E (Slp1-Emp65) complex captures misfolded and perhaps chaperone-bound folding intermediates of both glycosylated and unglycosylated (not shown) polypeptides soon after synthesis and prohibits premature ERAD. The capture of these off-pathway intermediates may provide both an extended timeframe and a folding platform to facilitate folding. Prior to SE complex capture and/or ERAD (left), glycan trimming exposes a terminal α-1,6-linked mannose residue in misfolded proteins, which triggers the binding of Yos9 and ERAD (Quan et al., 2008). The α-1,6-linked terminal mannose residue (denoted with a red triangle) is also appended directly to a polypeptide in an alg3Δ strain. In both cases, a population of misfolded proteins is captured by the S-E complex. Ultimately, soluble ERAD substrates are delivered to the Hrd1 complex for retrotranslocation and degradation by the 26S proteasome. Of note, it is unknown if Yos9 and other chaperones bind misfolded substrates in conjunction with the S-E complex and if terminally misfolded proteins bound by the complex are invariably targeted for ERAD or re-enter the folding pathway. Regardless, once folded, coat protein complex II (COPII) components initiate ER exit and transport to the Golgi (right). Cell 2017 171, 267-268DOI: (10.1016/j.cell.2017.09.023) Copyright © 2017 Elsevier Inc. Terms and Conditions