Spontaneous transmembrane helix insertion thermodynamically mimics translocon-guided insertion

Martin B Ulmschneider; Jakob P Ulmschneider; Nina Schiller; B A Wallace; Gunnar von Heijne; Stephen H White

doi:10.1038/ncomms5863

Spontaneous transmembrane helix insertion thermodynamically mimics translocon-guided insertion

Martin B Ulmschneider, Jakob P Ulmschneider, Nina Schiller, B A Wallace, Gunnar von Heijne, Stephen H White

Chemistry

Institute of Natural Sciences and Department of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai 200240, China.
1] Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden [2] Science for Life Laboratory, Stockholm University, SE-17177 Solna, Sweden.
Birkbeck, University of London
University of California, Irvine

Research output: Contribution to journal › Article › peer-review

85 Citations (Scopus)

Abstract

The favourable transfer free energy for a transmembrane (TM) α-helix between the aqueous phase and lipid bilayer underlies the stability of membrane proteins. However, the connection between the energetics and process of membrane protein assembly by the Sec61/SecY translocon complex in vivo is not clear. Here, we directly determine the partitioning free energies of a family of designed peptides using three independent approaches: an experimental microsomal Sec61 translocon assay, a biophysical (spectroscopic) characterization of peptide insertion into hydrated planar lipid bilayer arrays, and an unbiased atomic-detail equilibrium folding-partitioning molecular dynamics simulation. Remarkably, the measured free energies of insertion are quantitatively similar for all three approaches. The molecular dynamics simulations show that TM helix insertion involves equilibrium with the membrane interface, suggesting that the interface may play a role in translocon-guided insertion.

Original language	English
Article number	4863
Journal	Nature Communications
Volume	5
Early online date	10 Sept 2014
DOIs	https://doi.org/10.1038/ncomms5863
Publication status	Published - 10 Sept 2014

Keywords

Amino Acid Motifs
Cell Membrane/metabolism
Escherichia coli Proteins/metabolism
Membrane Proteins/metabolism
Molecular Dynamics Simulation
Protein Structure, Secondary
SEC Translocation Channels
Serine Endopeptidases/metabolism
Spectrum Analysis
Thermodynamics

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title = "Spontaneous transmembrane helix insertion thermodynamically mimics translocon-guided insertion",

abstract = "The favourable transfer free energy for a transmembrane (TM) α-helix between the aqueous phase and lipid bilayer underlies the stability of membrane proteins. However, the connection between the energetics and process of membrane protein assembly by the Sec61/SecY translocon complex in vivo is not clear. Here, we directly determine the partitioning free energies of a family of designed peptides using three independent approaches: an experimental microsomal Sec61 translocon assay, a biophysical (spectroscopic) characterization of peptide insertion into hydrated planar lipid bilayer arrays, and an unbiased atomic-detail equilibrium folding-partitioning molecular dynamics simulation. Remarkably, the measured free energies of insertion are quantitatively similar for all three approaches. The molecular dynamics simulations show that TM helix insertion involves equilibrium with the membrane interface, suggesting that the interface may play a role in translocon-guided insertion. ",

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AU - Ulmschneider, Martin B

AU - Ulmschneider, Jakob P

AU - Schiller, Nina

AU - Wallace, B A

AU - von Heijne, Gunnar

AU - White, Stephen H

PY - 2014/9/10

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N2 - The favourable transfer free energy for a transmembrane (TM) α-helix between the aqueous phase and lipid bilayer underlies the stability of membrane proteins. However, the connection between the energetics and process of membrane protein assembly by the Sec61/SecY translocon complex in vivo is not clear. Here, we directly determine the partitioning free energies of a family of designed peptides using three independent approaches: an experimental microsomal Sec61 translocon assay, a biophysical (spectroscopic) characterization of peptide insertion into hydrated planar lipid bilayer arrays, and an unbiased atomic-detail equilibrium folding-partitioning molecular dynamics simulation. Remarkably, the measured free energies of insertion are quantitatively similar for all three approaches. The molecular dynamics simulations show that TM helix insertion involves equilibrium with the membrane interface, suggesting that the interface may play a role in translocon-guided insertion.

AB - The favourable transfer free energy for a transmembrane (TM) α-helix between the aqueous phase and lipid bilayer underlies the stability of membrane proteins. However, the connection between the energetics and process of membrane protein assembly by the Sec61/SecY translocon complex in vivo is not clear. Here, we directly determine the partitioning free energies of a family of designed peptides using three independent approaches: an experimental microsomal Sec61 translocon assay, a biophysical (spectroscopic) characterization of peptide insertion into hydrated planar lipid bilayer arrays, and an unbiased atomic-detail equilibrium folding-partitioning molecular dynamics simulation. Remarkably, the measured free energies of insertion are quantitatively similar for all three approaches. The molecular dynamics simulations show that TM helix insertion involves equilibrium with the membrane interface, suggesting that the interface may play a role in translocon-guided insertion.

KW - Amino Acid Motifs

KW - Cell Membrane/metabolism

KW - Escherichia coli Proteins/metabolism

KW - Membrane Proteins/metabolism

KW - Molecular Dynamics Simulation

KW - Protein Structure, Secondary

KW - SEC Translocation Channels

KW - Serine Endopeptidases/metabolism

KW - Spectrum Analysis

KW - Thermodynamics

U2 - 10.1038/ncomms5863

DO - 10.1038/ncomms5863

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SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

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ER -

Spontaneous transmembrane helix insertion thermodynamically mimics translocon-guided insertion

Abstract

Keywords

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