title: Folding and self-assembly of the TatA translocation pore based on a charge zipper mechanism.
abstract: We propose a concept for the folding and self-assembly of the pore-forming TatA complex from the Twin-arginine translocase and of other membrane proteins based on electrostatic "charge zippers." Each subunit of TatA consists of a transmembrane segment, an amphiphilic helix (APH), and a C-terminal densely charged region (DCR). The sequence of charges in the DCR is complementary to the charge pattern on the APH, suggesting that the protein can be "zipped up" by a ladder of seven salt bridges. The length of the resulting hairpin matches the lipid bilayer thickness, hence a transmembrane pore could self-assemble via intra- and intermolecular salt bridges. The steric feasibility was rationalized by molecular dynamics simulations, and experimental evidence was obtained by monitoring the monomer-oligomer equilibrium of specific charge mutants. Similar "charge zippers" are proposed for other membrane-associated proteins, e.g., the biofilm-inducing peptide TisB, the human antimicrobial peptide dermcidin, and the pestiviral E(RNS) protein.
authors: Karlsruhe Institute of Technology, Institute of Biological Interfaces, Institute of Organic Chemistry and CFN, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
authors: Torsten H
authors: TH
authors: Walther
authors: Christina
authors: C
authors: Gottselig
authors: Stephan L
authors: SL
authors: Grage
authors: Moritz
authors: M
authors: Wolf
authors: Attilio V
authors: AV
authors: Vargiu
authors: Marco J
authors: MJ
authors: Klein
authors: Stefanie
authors: S
authors: Vollmer
authors: Sebastian
authors: S
authors: Prock
authors: Mareike
authors: M
authors: Hartmann
authors: Sergiy
authors: S
authors: Afonin
authors: Eva
authors: E
authors: Stockwald
authors: Hartmut
authors: H
authors: Heinzmann
authors: Olga V
authors: OV
authors: Nolandt
authors: Wolfgang
authors: W
authors: Wenzel
authors: Paolo
authors: P
authors: Ruggerone
authors: Anne S
authors: AS
authors: Ulrich
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D010455:Peptides; C499697:TatA protein, E coli; C575529:TisB toxin, E coli; D014764:Viral Proteins; C442243:dermcidin