Heinrich Sven U, Rapoport Tom A
Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
EMBO J. 2003 Jul 15;22(14):3654-63. doi: 10.1093/emboj/cdg346.
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.
虽然单跨膜蛋白插入内质网（ER）的过程相对较为清楚，但多跨膜蛋白如何整合尚不清楚。我们研究了一种源自前导肽酶的双跨膜蛋白的共翻译内质网整合过程。两个跨膜（TM）片段均通过Sec61通道插入膜中。第一个长且疏水的TM片段（TM1）独自插入脂质双层，而第二个较短的TM锚定片段（TM2）在整合过程中与TM1协同作用。在没有TM2的情况下，TM1从Sec61复合物扩散离开，但当TM2进入通道内部时，TM1靠近Sec61。这些数据表明，一个较弱的TM片段从Sec61通道进入脂质相的过程可通过其与先前整合的强且稳定的TM锚定片段的相互作用而得到促进。
