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Cooperation of transmembrane segments during the integration of a double‐spanning protein into the ER membrane
Author(s) -
Heinrich Sven U.,
Rapoport Tom A.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg346
Subject(s) - biology , transmembrane protein , membrane protein , microbiology and biotechnology , membrane , biophysics , computational biology , biochemistry , receptor
While membrane insertion of single‐spanning membrane proteins into the endoplasmic reticulum (ER) is relatively well understood, it is unclear how multi‐spanning proteins integrate. We have investigated the cotranslational ER integration of a double‐spanning protein that is derived from leader peptidase. Both transmembrane (TM) segments are inserted into the membrane by the Sec61 channel. While the first, long and hydrophobic TM segment (TM1) inserts into the lipid bilayer on its own, the second, shorter TM anchor (TM2) collaborates with TM1 during its integration. TM1 diffuses away from the Sec61 complex in the absence of TM2, but is close to Sec61 when TM2 arrives inside the channel. These data suggest that the exit of a weak TM segment from the Sec61 channel into the lipid phase can be facilitated by its interaction with a previously integrated strong and stabilizing TM anchor.