Publication

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.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Koch, S., Exterkate, M., López, C. A., Patro, M., Marrink, S. J., & Driessen, A. J. M. (2019). Two distinct anionic phospholipid-dependent events involved in SecA-mediated protein translocation. Biochimica et Biophysica Acta - Biomembranes, 1861(11), [183035]. https://doi.org/10.1016/j.bbamem.2019.183035

Author

Koch, Sabrina ; Exterkate, Marten ; López, Cesar A ; Patro, Megha ; Marrink, Siewert J ; Driessen, Arnold J M. / Two distinct anionic phospholipid-dependent events involved in SecA-mediated protein translocation. In: Biochimica et Biophysica Acta - Biomembranes. 2019 ; Vol. 1861, No. 11.

Harvard

Koch, S, Exterkate, M, López, CA, Patro, M, Marrink, SJ & Driessen, AJM 2019, 'Two distinct anionic phospholipid-dependent events involved in SecA-mediated protein translocation', Biochimica et Biophysica Acta - Biomembranes, vol. 1861, no. 11, 183035. https://doi.org/10.1016/j.bbamem.2019.183035

Standard

Two distinct anionic phospholipid-dependent events involved in SecA-mediated protein translocation. / Koch, Sabrina; Exterkate, Marten; López, Cesar A; Patro, Megha; Marrink, Siewert J; Driessen, Arnold J M.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1861, No. 11, 183035, 01.11.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Koch S, Exterkate M, López CA, Patro M, Marrink SJ, Driessen AJM. Two distinct anionic phospholipid-dependent events involved in SecA-mediated protein translocation. Biochimica et Biophysica Acta - Biomembranes. 2019 Nov 1;1861(11). 183035. https://doi.org/10.1016/j.bbamem.2019.183035


BibTeX

@article{431e32fee67b4fcc9398b781b7e8fa4f,
title = "Two distinct anionic phospholipid-dependent events involved in SecA-mediated protein translocation",
abstract = "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.",
author = "Sabrina Koch and Marten Exterkate and L{\'o}pez, {Cesar A} and Megha Patro and Marrink, {Siewert J} and Driessen, {Arnold J M}",
note = "Copyright {\circledC} 2019. Published by Elsevier B.V.",
year = "2019",
month = "11",
day = "1",
doi = "10.1016/j.bbamem.2019.183035",
language = "English",
volume = "1861",
journal = "Biochimica et Biophysica Acta - Biomembranes",
issn = "1879-2642",
number = "11",

}

RIS

TY - JOUR

T1 - Two distinct anionic phospholipid-dependent events involved in SecA-mediated protein translocation

AU - Koch, Sabrina

AU - Exterkate, Marten

AU - López, Cesar A

AU - Patro, Megha

AU - Marrink, Siewert J

AU - Driessen, Arnold J M

N1 - Copyright © 2019. Published by Elsevier B.V.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.bbamem.2019.183035

DO - 10.1016/j.bbamem.2019.183035

M3 - Article

VL - 1861

JO - Biochimica et Biophysica Acta - Biomembranes

JF - Biochimica et Biophysica Acta - Biomembranes

SN - 1879-2642

IS - 11

M1 - 183035

ER -

ID: 94202318