Membrane protein folding and quality control

Abstract

Membrane proteins account for a quarter of cellular proteins, and most are synthesised at the endoplasmic reticulum (ER). Insertion and folding of polypeptides in the membrane environment is prone to error, necessitating diverse quality control systems. Recent discoveries have demonstrated how forces act on the nascent chain during insertion, and revealed new translocon components and accessories that facilitate the correct biogenesis of substrates. Our understanding of one of the best studied quality control systems—ER-associated degradation—has been advanced through new structural and functional studies of the core Hrd1 complex, and through the discovery of a new branch of this degradative pathway. New data also reveal how cells resolve clogged translocons, which would otherwise be unable to function. Finally, new work elucidates how mitochondrial tail-anchored proteins that have been mistargeted to the ER are identified and destroyed. Overall, we describe an emerging picture of an increasingly complex quality control network.

Lysosome docking to WIPI1 rings and ER-connected phagophores occurs during DNAJB12- and GABARAP-dependent selective autophagy of misfolded P23H-rhodopsin

“…The endoplasmic reticulum (ER) is the site where biogenesis of membrane proteins initiates in a process that requires the coordinated folding and assembly of subdomains that are located in the cytosol, lumen, and ER membrane ( Phillips and Miller, 2021 ). This process can be inefficient for both wild-type (WT) and disease proteins, which challenge ER protein quality control (ERQC) systems with the accumulation of potentially toxic misfolded intermediates ( Hipp et al.…”

Comparative transcriptome and proteome reveal synergistic functions of differentially expressed genes and proteins implicated in an over‐dominant silkworm heterosis of increased silk yield

“…Human Ebp1 plays important role in cancer regulation, and up‐regulation of it can promote the biosynthesis of rRNA and ribosome and enhance protein translation to promote cell proliferation, while its depletion can greatly reduce rRNA synthesis and cell proliferation (Nguyen et al, 2016). Sec61 alpha is the core and channel‐forming sub‐unit of the protein translocon Sec61, which is responsible for the translocation of newly synthesized proteins across rough ER (Phillips & Miller, 2021). Interestingly, Sec61 beta subunit and two translocon‐associated proteins but not Sec61 alpha have been shown to be down‐regulated in the low‐yield mutant ZB compared to the high‐yield control Lan10 (S. Wang et al, 2016), indicating a positive correlation of translocon with silk yield despite the difference possibly due to variance in samples and strains.…”

S‐acylation: an orchestrator of the life cycle and function of membrane proteins

“…With the notable exception of tail-anchored proteins, transmembrane proteins of the endomembrane system are synthesized by ribosomes that dock onto translocons present in the rough ER, and are then cotranslationally inserted into the membrane. The luminal/ extracellular domains undergo PTMs in the ER and benefit from an arsenal of luminal folding assisting proteins -for example, chaperones, protein disulfide isomerases, and proline isomerases, as do secretory proteins [76].…”