ER-associated degradation articles within Nature Communications

Featured

• Article
  11 March 2024 | Open Access

  Substrate recognition mechanism of the endoplasmic reticulum-associated ubiquitin ligase Doa10

  Doa10/MARCHF6 is a conserved E3 ubiquitin ligase in the endoplasmic reticulum (ER) membrane in eukaryotes, but its molecular mechanism was unknown. The authors combine cryo-EM, computational and biochemical analyses to reveal how Doa10 recognizes its substrate proteins for ER-associated degradation.

  • Kevin Wu
  • , Samuel Itskanov
  •  & Eunyong Park

• Article
  07 March 2024 | Open Access

  RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling

  Toll-like receptor 4 (TLR4) is a key pattern recognition receptor that primarily responds to ligation of bacterial lipopolysaccharide. Here the authors suggest the intramembrane protease RHBDL4 as a regulator of TLR4 signaling.

  • Julia D. Knopf
  • , Susanne S. Steigleder
  •  & Marius K. Lemberg

• Article
  16 February 2024 | Open Access

  SEL1L-HRD1 interaction is required to form a functional HRD1 ERAD complex

  The importance of the SEL1L-HRD1 interaction in vivo was unclear. Here, authors reported that SEL1L-HRD1 interaction is required to form a functional HRD1 ERAD complex by recruiting the E2 enzyme UBE2J1 and DERLIN to HRD1.

  • Liangguang Leo Lin
  • , Huilun Helen Wang
  •  & Ling Qi

• Article
  13 February 2024 | Open Access

  Direct observation of autoubiquitination for an integral membrane ubiquitin ligase in ERAD

  The stoichiometry of Hrd1, an integral membrane E3 ubiquitin ligase is critical to maintaining proteostasis in the endoplasmic reticulum. Here, the authors establish a single-molecule counting approach coupled with a single-molecule in vitro ubiquitination system to determine the functional stoichiometry of Hrd1.

  • Basila Moochickal Assainar
  • , Kaushik Ragunathan
  •  & Ryan D. Baldridge

• Article
  22 January 2024 | Open Access

  Proteomic screens of SEL1L-HRD1 ER-associated degradation substrates reveal its role in glycosylphosphatidylinositol-anchored protein biogenesis

  The nature of SEL1L-HRD1 ERAD substrates remains unclear. Here, the authors identified ~100 endogenous substrates, and showed that SEL1L-HRD1 ERAD is indispensable for the activity of GPI transamidase complex and the biogenesis of GPI-anchored proteins.

  • Xiaoqiong Wei
  • , You Lu
  •  & Ling Qi

• Article
  06 April 2021 | Open Access

  A slowly cleaved viral signal peptide acts as a protein-integral immune evasion domain

  Glycoprotein US9 of human cytomegalovirus downregulates the activating immune ligand MICA*008 to avoid NK cell activation. Here, Seidel et al. show that the signal peptide of US9 is cleaved unusually slowly, causing MICA*008 to be retained in the endoplasmic reticulum (ER) and degraded via the ER quality control system.

  • Einat Seidel
  • , Liat Dassa
  •  & Ofer Mandelboim

• Article
  13 February 2020 | Open Access

  Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation

  Glycosylphosphatidylinositol (GPI) anchors are found on many cell surface proteins but their biosynthesis is not fully understood. Here, the authors identify genes involved in GPI galactosylation and reveal functional connections between GPI processing, glycosphingolipid biosynthesis and ER-associated degradation.

  • Yicheng Wang
  • , Yusuke Maeda
  •  & Taroh Kinoshita

• Article
  06 February 2017 | Open Access

  Ufd2p synthesizes branched ubiquitin chains to promote the degradation of substrates modified with atypical chains

  How ubiquitination affects the proteins it modifies varies according to the type of linkage between ubiquitin moieties. Here, Liuet al. show how yeast Udf2p promotes K48 linkage formation onto K29-linked chains to generate branched K29-K48 ubiquitin chains that target its substrate to the proteasome.

  • Chao Liu
  • , Weixiao Liu
  •  & Wei Li

• Article
  20 October 2016 | Open Access

  Quantitative interaction mapping reveals an extended UBX domain in ASPL that disrupts functional p97 hexamers

  The AAA+ ATPase p97 is an essential hexameric protein with multiple protein interaction partners and cellular functions. Here, the authors use interaction mapping to examine partner proteins of this large complex, and assess the effects of these proteins on the disassembly of the p97 complex.

  • Anup Arumughan
  • , Yvette Roske
  •  & Erich E. Wanker

• Article
  04 May 2016 | Open Access

  TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis

  A cellular protease, SPP, participates in production of the mature core protein of hepatitis C virus (HCV). Here, the authors show in mouse models that SPP inhibition reduces viral propagation and pathogenesis via proteasomal degradation of the immature core protein mediated by the E3 ubiquitin ligase TRC8.

  • Sayaka Aizawa
  • , Toru Okamoto
  •  & Yoshiharu Matsuura

• Article
  08 May 2014 | Open Access

  A high-coverage shRNA screen identifies TMEM129 as an E3 ligase involved in ER-associated protein degradation

  The human cytomegalovirus protein US11 downregulates host immune responses by redirecting HLA class I molecules for endoplasmic reticulum-associated protein degradation. Using a high-coverage genome-wide shRNA screen, the authors identify TMEM129 as an E3 ubiquitin ligase essential for this process.

  • Michael L. van de Weijer
  • , Michael C. Bassik
  •  & Robert Jan Lebbink

• Article | 12 July 2011

  TorsinA participates in endoplasmic reticulum-associated degradation

  The torsinA protein localizes to the endoplasmic reticulum and, when mutated, causes early onset torsion dystonia. The authors reveal a new role for torsinA in proteosome-mediated degradation of misfolded proteins, and relate this to endoplasmic reticulum stress, in aCaenorhabditis elegansmodel and patient fibroblasts.

  • Flávia C. Nery
  • , Ioanna A. Armata
  •  & Xandra O. Breakefield