Competition between neighboring topogenic signals during membrane protein insertion into the ER |
| |
Authors: | Monné Magnus Hessa Tara Thissen Laura von Heijne Gunnar |
| |
Institution: | Department of Biochemistry and Biophysics, Stockholm University, Sweden. |
| |
Abstract: | To better define the mechanism of membrane protein insertion into the membrane of the endoplasmic reticulum, we measured the kinetics of translocation across microsomal membranes of the N-terminal lumenal tail and the lumenal domain following the second transmembrane segment (TM2) in the multispanning mouse protein Cig30. In the wild-type protein, the N-terminal tail translocates across the membrane before the downstream lumenal domain. Addition of positively charged residues to the N-terminal tail dramatically slows down its translocation and allows the downstream lumenal domain to translocate at the same time as or even before the N-tail. When TM2 is deleted, or when the loop between TM1 and TM2 is lengthened, addition of positively charged residues to the N-terminal tail causes TM1 to adopt an orientation with its N-terminal end in the cytoplasm. We suggest that the topology of the TM1-TM2 region of Cig30 depends on a competition between TM1 and TM2 such that the transmembrane segment that inserts first into the ER membrane determines the final topology. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|