Co- and post-translational protein folding in the ER

Lars Ellgaard; Nicholas McCaul; Anna Chatsisvili; Ineke Braakman

doi:10.1111/tra.12392

Co- and post-translational protein folding in the ER

Lars Ellgaard, Nicholas McCaul, Anna Chatsisvili, Ineke Braakman

Biomolecular Sciences

55 Citations (Scopus)

Abstract

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. Here, we review chaperone-assisted co- and post-translational folding and assembly in the ER and the influence of protein modifications, emphasizing how method development has advanced the field by allowing folding studies inside living cells. The laboratory of Dr Ari Helenius pioneered many of these studies with the influenza virus hemagglutinin (HA) protein, which is a trimer. This cartoon of an HA monomer drawn by Dr Ari Helenius shows the receptor domain (R), the esterase-like domain (E′) and the stem domain (S). Native HA has six disulfide bonds (orange lines). A, B, E, F1 and F2 indicate the positions of antigenic epitopes. 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.

Original language	English
Journal	Traffic (Malden)
Volume	17
Issue number	6
Pages (from-to)	615-638
Number of pages	24
ISSN	1398-9219
DOIs	https://doi.org/10.1111/tra.12392
Publication status	Published - 1 Jun 2016

Access to Document

10.1111/tra.12392

Cite this

@article{bd40df1ca8a94feba54fc94a6fe45e7f,

title = "Co- and post-translational protein folding in the ER",

abstract = "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. Here, we review chaperone-assisted co- and post-translational folding and assembly in the ER and the influence of protein modifications, emphasizing how method development has advanced the field by allowing folding studies inside living cells. The laboratory of Dr Ari Helenius pioneered many of these studies with the influenza virus hemagglutinin (HA) protein, which is a trimer. This cartoon of an HA monomer drawn by Dr Ari Helenius shows the receptor domain (R), the esterase-like domain (E′) and the stem domain (S). Native HA has six disulfide bonds (orange lines). A, B, E, F1 and F2 indicate the positions of antigenic epitopes. 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.",

author = "Lars Ellgaard and Nicholas McCaul and Anna Chatsisvili and Ineke Braakman",

note = "Special Issue: Viruses, protein folding and endocytosis: a special issue dedicated to Ari Helenius",

year = "2016",

month = jun,

day = "1",

doi = "10.1111/tra.12392",

language = "English",

volume = "17 ",

pages = "615--638",

journal = "Traffic",

issn = "1398-9219",

publisher = "Wiley-Blackwell",

number = "6",

}

TY - JOUR

T1 - Co- and post-translational protein folding in the ER

AU - Ellgaard, Lars

AU - McCaul, Nicholas

AU - Chatsisvili, Anna

AU - Braakman, Ineke

N1 - Special Issue: Viruses, protein folding and endocytosis: a special issue dedicated to Ari Helenius

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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. Here, we review chaperone-assisted co- and post-translational folding and assembly in the ER and the influence of protein modifications, emphasizing how method development has advanced the field by allowing folding studies inside living cells. The laboratory of Dr Ari Helenius pioneered many of these studies with the influenza virus hemagglutinin (HA) protein, which is a trimer. This cartoon of an HA monomer drawn by Dr Ari Helenius shows the receptor domain (R), the esterase-like domain (E′) and the stem domain (S). Native HA has six disulfide bonds (orange lines). A, B, E, F1 and F2 indicate the positions of antigenic epitopes. 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.

AB - 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. Here, we review chaperone-assisted co- and post-translational folding and assembly in the ER and the influence of protein modifications, emphasizing how method development has advanced the field by allowing folding studies inside living cells. The laboratory of Dr Ari Helenius pioneered many of these studies with the influenza virus hemagglutinin (HA) protein, which is a trimer. This cartoon of an HA monomer drawn by Dr Ari Helenius shows the receptor domain (R), the esterase-like domain (E′) and the stem domain (S). Native HA has six disulfide bonds (orange lines). A, B, E, F1 and F2 indicate the positions of antigenic epitopes. 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.

U2 - 10.1111/tra.12392

DO - 10.1111/tra.12392

M3 - Review

C2 - 26947578

SN - 1398-9219

VL - 17

SP - 615

EP - 638

JO - Traffic

JF - Traffic

IS - 6

ER -

Co- and post-translational protein folding in the ER

Abstract

Access to Document

Fingerprint

Cite this