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Title: Structure of the Get3 targeting factor in complex with its membrane protein cargo

Tail-anchored (TA) proteins are a physiologically important class of membrane proteins targeted to the endoplasmic reticulum by the conserved guided-entry of TA proteins (GET) pathway. During transit, their hydrophobic transmembrane domains (TMDs) are chaperoned by the cytosolic targeting factor Get3, but the molecular nature of the functional Get3-TA protein targeting complex remains unknown. In this paper, we reconstituted the physiologic assembly pathway for a functional targeting complex and showed that it comprises a TA protein bound to a Get3 homodimer. Crystal structures of Get3 bound to different TA proteins showed an α-helical TMD occupying a hydrophobic groove that spans the Get3 homodimer. Finally, our data elucidate the mechanism of TA protein recognition and shielding by Get3 and suggest general principles of hydrophobic domain chaperoning by cellular targeting factors.
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [1]
  1. Univ. of Chicago, IL (United States). Dept. of Biochemistry and Molecular Biology
  2. MRC Lab. of Molecular Biology, Cambridge (United Kingdom)
Publication Date:
OSTI Identifier:
Grant/Contract Number:
AC02-06CH11357; P41 GM103403; MC_UP_A022_1007; U01 GM094588; U54 GM087519; R01 GM086487
Accepted Manuscript
Journal Name:
Additional Journal Information:
Journal Volume: 347; Journal Issue: 6226; Journal ID: ISSN 0036-8075
Research Org:
Univ. of Chicago, IL (United States); MRC Lab. of Molecular Biology, Cambridge (United Kingdom)
Sponsoring Org:
USDOE; National Inst. of Health (NIH) (United States); Medical Research Council (MRC) (United Kingdom)
Country of Publication:
United States