The BioGRID | PUBLICATION VIEW

	J. Biol. Chem. Nov (2007); 282(45):33201-9
Mutations in the sec61p channel affecting signal sequence recognition and membrane protein topology-
Junne T, Schwede T, Goder V, Spiess M
Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland-
Abstract: The orientation of most single-spanning membrane proteins obeys the "positive-inside rule", i-e- the flanking region of the transmembrane segment that is more positively charged remains in the cytosol- These membrane proteins are integrated by the Sec61-SecY translocon, but how their orientation is achieved is unknown- We have screened for mutations in yeast Sec61p that alter the orientation of single-spanning membrane proteins- We identified a class of mutants that are less efficient in retaining the positively charged flanking region in the cytosol- Surprisingly, these mutations are located at many different sites in the Sec61-SecY molecule, and they do not only involve charged amino acid residues- All these mutants have a prl phenotype that so far have only been seen in bacteria; they allow proteins with defective signal sequences to be translocated, likely because the Sec61p channel opens more easily- A similar correlation between topology defects and prl phenotype was also seen with previously identified yeast Sec61 mutants- Our results suggest a model in which the regulated opening of the translocon is required for the faithful orientation of membrane proteins-
[PUBMED: 17893139]