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Two distinct anionic phospholipid-dependent events involved in SecA-mediated protein translocation

Koch, S., Exterkate, M., López, C. A., Patro, M., Marrink, S. J. & Driessen, A. J. M., 1-Nov-2019, In : Biochimica et Biophysica Acta - Biomembranes. 1861, 11, 183035.

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  • Two distinct anionic phospholipid-dependent events involved in SecA-mediated protein translocation

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DOI

Protein translocation across the bacterial cytoplasmic membrane is an essential process catalyzed by the Sec translocase, which in its minimal form consists of the protein-conducting channel SecYEG, and the motor ATPase SecA. SecA binds via its positively charged N-terminus to membranes containing anionic phospholipids, leading to a lipid-bound intermediate. This interaction induces a conformational change in SecA, resulting in a high-affinity association with SecYEG, which initiates protein translocation. Here, we examined the effect of anionic lipids on the SecA-SecYEG interaction in more detail, and discovered a second, yet unknown, anionic lipid-dependent event that stimulates protein translocation. Based on molecular dynamics simulations we identified an anionic lipid-enriched region in vicinity of the lateral gate of SecY. Here, the anionic lipid headgroup accesses the lateral gate, thereby stabilizing the pre-open state of the channel. The simulations suggest flip-flop movement of phospholipid along the lateral gate. Electrostatic contribution of the anionic phospholipids at the lateral gate may directly stabilize positively charged residues of the signal sequence of an incoming preprotein. Such a mechanism allows for the correct positioning of the entrant peptide, thereby providing a long-sought explanation for the role of anionic lipids in signal sequence folding during protein translocation.

Original languageEnglish
Article number183035
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1861
Issue number11
Early online date5-Aug-2019
Publication statusPublished - 1-Nov-2019

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