+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Membrane chaperone Shr3 assists in folding amino acid permeases preventing precocious ERAD



Membrane chaperone Shr3 assists in folding amino acid permeases preventing precocious ERAD



Journal of Cell Biology 176(5): 617-628



The yeast endoplasmic reticulum (ER) membrane-localized chaperone Shr3 plays a critical role in enabling amino acid permeases (AAPs) to fold and attain proper structures required for functional expression at the plasma membrane. In the absence of Shr3, AAPs specifically accumulate in the ER, where despite the correct insertion of their 12 transmembrane segments (TMSs), they aggregate forming large molecular weight complexes. We show that Shr3 prevents aggregation and facilitates the functional assembly of independently coexpressed N- and C-terminal fragments of the general AAP Gap1. Shr3 interacts with and maintains the first five TMSs in a conformation that can posttranslationally assemble with the remaining seven TMSs. We also show that Doa10- and Hrd1-dependent ER-associated degradation (ERAD) pathways redundantly degrade AAP aggregates. In combination, doa10Delta hrd1Delta mutations stabilize AAP aggregates and partially suppress amino acid uptake defects of shr3 mutants. Consequently, in cells with impaired ERAD, AAPs are able to attain functional conformations independent of Shr3. These findings illustrate that folding and degradation are tightly coupled processes during membrane protein biogenesis.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 012991869

Download citation: RISBibTeXText

PMID: 17325204

DOI: 10.1083/jcb.200612100


Related references

Membrane Chaperone Shr3 Assists in Folding Amino Acid Permeases Preventing Precocious Erad. The Journal of Cell Biology 176(5): 617-628, 2007

The molecular function of SHR3 in the packaging of amino acid permeases into ER-derived COPII vesicles. Folia Microbiologica 44(2): 224, 1999

SHR3: A novel component of the secretory pathway specifically required for localization of amino acid permeases in yeast. Cell 71(3): 463-478, 1992

The folding and membrane topology of GAP1 is independent of SHR3 function. Folia Microbiologica 42(3): 261-262, 1997

The molecular chaperone Hsc70 assists the in vitro folding of the N-terminal nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator. Journal of Biological Chemistry 272(41): 25421-4, 1997

The antifungal eugenol perturbs dual aromatic and branched-chain amino acid permeases in the cytoplasmic membrane of yeast. Plos one 8(10): E76028, 2013

Mutant human protein disulfide isomerase assists protein folding in a chaperone-like fashion. Journal Of Biotechnology. 54(2): 105-112, 1997

Amino acid permeases require COPII components and the ER resident membrane protein Shr3p for packaging into transport vesicles in vitro. Journal of cell biology 135(3): 585-595, 1996

SHR3 controls amino acid permease localization in yeast. Folia Microbiologica 42(3): 267, 1997

The reductase TMX1 contributes to ERAD by preferentially acting on membrane-associated folding-defective polypeptides. Biochemical and Biophysical Research Communications 503(2): 938-943, 2018

Amino acid residues important for substrate specificity of the amino acid permeases Can1p and Gnp1p in Saccharomyces cerevisiae. Yeast 18(15): 1429-1440, 2001

Insertion and folding of the amino-terminal amphiphilic signal sequences of the mannitol and glucitol permeases of Escherichia coli. Journal of Biological Chemistry 267(16): 11017-11022, 1992

Multiplicity of the amino acid permeases in Saccharomyces cerevisiae. IV. Evidence for a general amino acid permease. Journal of Bacteriology 103(3): 770-777, 1970

Amino acid permeases in developing seeds of Vicia faba L.: expression precedes storage protein synthesis and is regulated by amino acid supply. Plant Journal 28(1): 61-71, 2001

SurA assists the folding of Escherichia coli outer membrane proteins. Journal of Bacteriology 178(6): 1770-1773, 1996