title: Co- and Post-Translational Protein Folding in the ER.
abstract: The biophysical rules that govern folding of small, single-domain proteins in dilute solutions are now quite well understood. The mechanisms underlying co-translational folding of multidomain and membrane-spanning proteins in complex cellular environments are often less clear. The endoplasmic reticulum (ER) produces a plethora of membrane and secretory proteins, which must fold and assemble correctly before ER exit - if these processes fail, misfolded species accumulate in the ER or are degraded. The ER differs from other cellular organelles in terms of the physicochemical environment and the variety of ER-specific protein modifications. Here, we review chaperone-assisted co- and post-translational folding and assembly in the ER and underline the influence of protein modifications on these processes. We emphasize how method development has helped advance the field by allowing researchers to monitor the progression of folding as it occurs inside living cells, while at the same time probing the intricate relationship between protein modifications during folding.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Ellgaard
authors.affiliation: Cellular Protein Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Nicholas
authors.initials: N
authors.lastname: McCaul
authors.affiliation: Cellular Protein Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Chatsisvili
authors.affiliation: Cellular Protein Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ineke
authors.initials: I
authors.lastname: Braakman
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D017510:Protein Folding; D011499:Protein Processing, Post-Translational
chemical_list: D018832:Molecular Chaperones
keywords: N-glycosylation; chaperones; disulfide-bond formation; endoplasmic reticulum; folding enzymes; protein folding