title: Signal sequences specify the targeting route to the endoplasmic reticulum membrane.
abstract: In the yeast Saccharomyces cerevisiae, only a subset of preproteins that are translocated across the ER membrane require the function of the signal recognition particle (SRP), suggesting that an alternative, SRP-independent pathway must exist (Hann, B.C., and P. Walter. 1991. Cell. 67:131-144). We have established that the two targeting pathways function in parallel. Mutant alleles of SEC62 and SEC63 were isolated that specifically impaired the translocation of SRP-independent preproteins in vivo and in vitro, whereas SRP-dependent preproteins were unaffected. Based on this analysis, preproteins fall into three distinct classes: SRP dependent, SRP independent, and those that can use both pathways. Pathway specificity is conferred by the hydrophobic core of signal sequences. Our studies show a previously unrecognized diversity in ER-directed signal sequences, that carry structural information that serves to identify the route taken.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, School of Medicine, San Francisco 94143-0448, USA. ng@cgl.ucsf.edu
authors.forename: D T
authors.initials: DT
authors.lastname: Ng
authors.forename: J D
authors.initials: JD
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Walter
mesh_terms: D001483:Base Sequence; D001692:Biological Transport; D004271:DNA, Fungal; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D021382:Protein Sorting Signals / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D021382:Protein Sorting Signals; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C059010:dipeptidyl aminopeptidase B