A chaperone cascade sorts proteins for posttranslational membrane insertion into the endoplasmic reticulum

Fei Wang, Emily C. Brown, Gary Mak, Jimmy Zhuang, Vladimir Denic

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Tail-anchored (TA) proteins are posttranslationally inserted into either the endoplasmic reticulum (ER) or the mitochondrial outer membrane. The C-terminal transmembrane domains (TMDs) of TA proteins enable their many essential cellular functions by specifying the membrane target, but how cells process these targeting signals is poorly understood. Here, we reveal the composition of a conserved multiprotein TMD recognition complex (TRC) and show that distinct TRC subunits recognize the two types of TMD signals. By engineering mutations in a mitochondrial TMD, we switch over its TRC subunit recognition, thus leading to its misinsertion into the ER. Biochemical reconstitution with purified components demonstrates that TRC tethers and enzymatically activates Get3 to selectively hand off ER-bound TA proteins to Get3. Thus, ER-bound TA proteins are sorted at the top of a TMD chaperone cascade that culminates with the formation of Get3-TA protein complexes, which are recruited to the ER membrane for insertion.

Original languageEnglish (US)
Pages (from-to)159-171
Number of pages13
JournalMolecular cell
Volume40
Issue number1
DOIs
StatePublished - Oct 8 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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