Folding and self-assembly of the TatA translocation pore based on a charge zipper mechanism

Torsten, Hw;Gottselig, C;Grage, Sl;Wolf, M;VARGIU, ATTILIO VITTORIO;Klein, M.j.;Vollmer, S;Prock, S;Hartmann, M;Afonin, S;Stockwald, E;Heinzmann, H;Nolandt, Ov;Wenzel, W;RUGGERONE, PAOLO;Ulrich, As

2013-01-01

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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 ERNS protein.