title: Sec62 protein mediates membrane insertion and orientation of moderately hydrophobic signal anchor proteins in the endoplasmic reticulum (ER).
abstract: Nascent chains are known to be targeted to the endoplasmic reticulum membrane either by a signal recognition particle (SRP)-dependent co-translational or by an SRP-independent post-translational translocation route depending on signal sequences. Using a set of model and cellular proteins carrying an N-terminal signal anchor sequence of controlled hydrophobicity and yeast mutant strains defective in SRP or Sec62 function, the hydrophobicity-dependent targeting efficiency and targeting pathway preference were systematically evaluated. Our results suggest that an SRP-dependent co-translational and an SRP-independent post-translational translocation are not mutually exclusive for signal anchor proteins and that moderately hydrophobic ones require both SRP and Sec62 for proper targeting and translocation to the endoplasmic reticulum. Further, defect in Sec62 selectively reduced signal sequences inserted in an N(in)-C(out) (type II) membrane topology, implying an undiscovered role of Sec62 in regulating the orientation of the signal sequence in an early stage of translocation.
authors: School of Biological Sciences, Seoul National University, Seoul 151-747, Korea.
authors: Johannes H
authors: JH
authors: Reithinger
authors: Ji Eun Hani
authors: JE
authors: Kim
authors: Hyun
authors: H
authors: Kim
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000235:genetics; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D021382:Protein Sorting Signals; C074213:SEC62 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D018271:Signal Recognition Particle
keywords: Endoplasmic Reticulum (ER); Membrane Proteins; Protein Translocation; Sec61; Signal Recognition Particle; Topology; Yeast
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