Article
- The EMBO Journal (2005) 24, 2284 - 2293
- doi:10.1038/sj.emboj.7600731
Published online: 23 June 2005
Subject Categories:
The protein translocation channel binds proteasomes to the endoplasmic reticulum membrane
Kai-Uwe Kalies1, Susanne Allan1, Tatiana Sergeyenko2, Heike Kröger2 and Karin Römisch2
- Institute of Biology, University of Lübeck, Lübeck, Germany
- Department of Clinical Biochemistry and Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
Correspondence to:
Karin Römisch, Department of Clinical Biochemistry and Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK. E-mail: kbr20@cam.ac.uk
Received 21 April 2005; Accepted 7 June 2005
Abstract
Misfolded secretory proteins are transported across the endoplasmic reticulum (ER) membrane into the cytosol for degradation by proteasomes. A large fraction of proteasomes in a cell is associated with the ER membrane. We show here that binding of proteasomes to ER membranes is salt sensitive, ATP dependent, and mediated by the 19S regulatory particle. The base of the 19S particle, which contains six AAA-ATPases, binds to microsomal membranes with high affinity, whereas the 19S lid complex binds weakly. We demonstrate that ribosomes and proteasomes compete for binding to the ER membrane and have similar affinities for their receptor. Ribosomes bind to the protein conducting channel formed by the Sec61 complex in the ER membrane. We co-precipitated subunits of the Sec61 complex with ER-associated proteasome 19S particles, and found that proteoliposomes containing only the Sec61 complex retained proteasome binding activity. Collectively, our data suggest that the Sec61 channel is a principal proteasome receptor in the ER membrane.
Keywords:
- endoplasmic reticulum,
- ER-associated degradation,
- proteasome,
- protein translocation,
- Sec61 channel
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