title: Protein transport into the human endoplasmic reticulum.
abstract: Protein transport into the endoplasmic reticulum (ER) is essential for all eukaryotic cells and evolutionary related to protein transport into and across the cytoplasmic membrane of eubacteria and archaea. It is based on amino-terminal signal peptides in the precursor polypeptides plus various transport components in cytosol plus ER and can occur either cotranslationally or posttranslationally. The two mechanisms merge at the heterotrimeric Sec61 complex in the ER membrane, which forms an aqueous polypeptide-conducting channel. Since the mammalian ER is also the main intracellular calcium storage organelle, the Sec61 complex is tightly regulated in its dynamics between the open and closed conformations by various ligands, such as precursor polypeptides at the cytosolic face and the Hsp70-type molecular chaperone BiP at the ER lumenal face (Hsp, heat shock protein). Furthermore, BiP binding to the incoming precursor polypeptide contributes to unidirectionality and efficiency of transport. Recent insights into the structural dynamics of the Sec61 complex and related complexes in eubacteria and archaea have various mechanistic and functional implications.
authors: Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany.
authors: Johanna
authors: J
authors: Dudek
authors: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors: Stefan
authors: S
authors: Pfeffer
authors: Computational Biology, Saarland University, 66041 Saarbrücken, Germany.
authors: Po-Hsien
authors: PH
authors: Lee
authors: Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany.
authors: Martin
authors: M
authors: Jung
authors: Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421 Homburg, Germany.
authors: Adolfo
authors: A
authors: Cavalié
authors: Computational Biology, Saarland University, 66041 Saarbrücken, Germany.
authors: Volkhard
authors: V
authors: Helms
authors: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors: Friedrich
authors: F
authors: Förster
authors: Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany. Electronic address: richard.zimmermann@uks.eu.
authors: Richard
authors: R
authors: Zimmermann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D000069816:SEC Translocation Channels; D017386:Sequence Homology, Amino Acid
chemical_list: D008565:Membrane Proteins; D000069816:SEC Translocation Channels
keywords: Sec61 complex; driving forces; endoplasmic reticulum; membrane insertion; protein translocation