Insertion and folding pathways of single membrane proteins guided by translocases and insertases.
- Resource Type
- Academic Journal
- Authors
- Serdiuk T; Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH)-Zürich, 4058 Basel, Switzerland.; Steudle A; Institute of Microbiology and Molecular Biology, University of Hohenheim, 70599 Stuttgart, Germany.; Mari SA; Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH)-Zürich, 4058 Basel, Switzerland.; Manioglu S; Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH)-Zürich, 4058 Basel, Switzerland.; Kaback HR; Department of Physiology, University of California, Los Angeles, Los Angeles, CA, USA.; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.; Kuhn A; Institute of Microbiology and Molecular Biology, University of Hohenheim, 70599 Stuttgart, Germany.; Müller DJ; Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH)-Zürich, 4058 Basel, Switzerland.
- Source
- Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: eCollection Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE
- Subject
- Language
- English
Biogenesis in prokaryotes and eukaryotes requires the insertion of α-helical proteins into cellular membranes for which they use universally conserved cellular machineries. In bacterial inner membranes, insertion is facilitated by YidC insertase and SecYEG translocon working individually or cooperatively. How insertase and translocon fold a polypeptide into the native protein in the membrane is largely unknown. We apply single-molecule force spectroscopy assays to investigate the insertion and folding process of single lactose permease (LacY) precursors assisted by YidC and SecYEG. Both YidC and SecYEG initiate folding of the completely unfolded polypeptide by inserting a single structural segment. YidC then inserts the remaining segments in random order, whereas SecYEG inserts them sequentially. Each type of insertion process proceeds until LacY folding is complete. When YidC and SecYEG cooperate, the folding pathway of the membrane protein is dominated by the translocase. We propose that both of the fundamentally different pathways along which YidC and SecYEG insert and fold a polypeptide are essential components of membrane protein biogenesis.