The BioGRID | PUBLICATION VIEW

	J. Cell Biol. Feb (2007); 176(5):617-28
Membrane chaperone Shr3 assists in folding amino acid permeases preventing precocious ERAD-
Kota J, Gilstring CF, Ljungdahl PO
Ludwig Institute for Cancer Research, S-17177 Stockholm, Sweden-
Abstract: 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-
[PUBMED: 17325204]