SPONTANEOUS TRANSMEMBRANE HELIX INSERTION THERMODYNAMICALLY MIMICS TRANSLOCON-GUIDED INSERTION

SPONTANEOUS TRANSMEMBRANE HELIX INSERTION THERMODYNAMICALLY MIMICS TRANSLOCON-GUIDED INSERTION

The favorable 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 cl...

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Main Authors: Ulmschneider, Martin B., Ulmschneider, Jakob P., Schiller, Nina, Wallace, B. A., von Heijne, Gunnar, White, Stephen H.
Format: Online
Language:English
Published: 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161982/
id pubmed-4161982
recordtype oai_dc
spelling pubmed-41619822015-03-10 SPONTANEOUS TRANSMEMBRANE HELIX INSERTION THERMODYNAMICALLY MIMICS TRANSLOCON-GUIDED INSERTION Ulmschneider, Martin B. Ulmschneider, Jakob P. Schiller, Nina Wallace, B. A. von Heijne, Gunnar White, Stephen H. Article The favorable 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. 2014-09-10 /pmc/articles/PMC4161982/ /pubmed/25204588 http://dx.doi.org/10.1038/ncomms5863 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ulmschneider, Martin B.
Ulmschneider, Jakob P.
Schiller, Nina
Wallace, B. A.
von Heijne, Gunnar
White, Stephen H.
spellingShingle Ulmschneider, Martin B.
Ulmschneider, Jakob P.
Schiller, Nina
Wallace, B. A.
von Heijne, Gunnar
White, Stephen H.
SPONTANEOUS TRANSMEMBRANE HELIX INSERTION THERMODYNAMICALLY MIMICS TRANSLOCON-GUIDED INSERTION
author_facet Ulmschneider, Martin B.
Ulmschneider, Jakob P.
Schiller, Nina
Wallace, B. A.
von Heijne, Gunnar
White, Stephen H.
author_sort Ulmschneider, Martin B.
title SPONTANEOUS TRANSMEMBRANE HELIX INSERTION THERMODYNAMICALLY MIMICS TRANSLOCON-GUIDED INSERTION
title_short SPONTANEOUS TRANSMEMBRANE HELIX INSERTION THERMODYNAMICALLY MIMICS TRANSLOCON-GUIDED INSERTION
title_full SPONTANEOUS TRANSMEMBRANE HELIX INSERTION THERMODYNAMICALLY MIMICS TRANSLOCON-GUIDED INSERTION
title_fullStr SPONTANEOUS TRANSMEMBRANE HELIX INSERTION THERMODYNAMICALLY MIMICS TRANSLOCON-GUIDED INSERTION
title_full_unstemmed SPONTANEOUS TRANSMEMBRANE HELIX INSERTION THERMODYNAMICALLY MIMICS TRANSLOCON-GUIDED INSERTION
title_sort spontaneous transmembrane helix insertion thermodynamically mimics translocon-guided insertion
description The favorable 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.
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161982/
_version_ 1613133290028400640

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