Tail-Anchored Protein Insertion into Yeast ER Requires a Novel Posttranslational Mechanism Which Is Independent of the SEC Machinery

Tail-anchored or C-terminally-anchored proteins play many essential roles in eukaryotic cells. However, targeting and insertion of this class of membrane protein has remained elusive. In this study, we reconstitute insertion of tail-anchored proteins into microsomes derived from Saccharomyces cerevi...

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Bibliographic Details
Published in:Biochemistry (Easton) 2002-10, Vol.41 (39), p.11914-11920
Main Authors: Steel, Gregor J, Brownsword, Judy, Stirling, Colin J
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - physiology
Endopeptidases
Endoplasmic Reticulum - genetics
Endoplasmic Reticulum - metabolism
HSP70 Heat-Shock Proteins - genetics
HSP70 Heat-Shock Proteins - metabolism
HSP70 Heat-Shock Proteins - physiology
Membrane Proteins - genetics
Membrane Proteins - metabolism
Microsomes - metabolism
Peptide Fragments - genetics
Peptide Fragments - metabolism
Protein Binding - genetics
Protein Precursors - genetics
Protein Precursors - metabolism
Protein Precursors - physiology
Protein Processing, Post-Translational - genetics
Protein Transport - genetics
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae - physiology
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
SNARE Proteins
Vacuoles - genetics
Vacuoles - metabolism
Vesicular Transport Proteins
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Summary:Tail-anchored or C-terminally-anchored proteins play many essential roles in eukaryotic cells. However, targeting and insertion of this class of membrane protein has remained elusive. In this study, we reconstitute insertion of tail-anchored proteins into microsomes derived from Saccharomyces cerevisiae. Using this approach, we are able to genetically manipulate the composition of the microsomes in order to address the question of which components of the endoplasmic reticulum (ER) are required for this process. We show that tail-anchored protein insertion is not dependent on the classical SEC translocation machinery but rather occurs via an ATP-dependent pathway involving at least one novel membrane protein factor. We further demonstrate that the specificity of this pathway is conserved between yeast and mammals.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi026105r