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All-Atom Molecular Dynamics Elucidating Molecular Mechanisms of Single-Transmembrane Model Peptide Dimerization in a Lipid Bilayer

[Image: see text] Protein–protein interactions between transmembrane helices are essential elements for membrane protein structures and functions. To understand the effects of peptide sequences and lipid compositions on these interactions, single-molecule experiments using model systems comprising a...

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Autores principales: Itaya, Hayato, Kasahara, Kota, Xie, Qilin, Yano, Yoshiaki, Matsuzaki, Katsumi, Takahashi, Takuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153988/
https://www.ncbi.nlm.nih.gov/pubmed/34056301
http://dx.doi.org/10.1021/acsomega.1c00482
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author Itaya, Hayato
Kasahara, Kota
Xie, Qilin
Yano, Yoshiaki
Matsuzaki, Katsumi
Takahashi, Takuya
author_facet Itaya, Hayato
Kasahara, Kota
Xie, Qilin
Yano, Yoshiaki
Matsuzaki, Katsumi
Takahashi, Takuya
author_sort Itaya, Hayato
collection PubMed
description [Image: see text] Protein–protein interactions between transmembrane helices are essential elements for membrane protein structures and functions. To understand the effects of peptide sequences and lipid compositions on these interactions, single-molecule experiments using model systems comprising artificial peptides and membranes have been extensively performed. However, their dynamic behavior at the atomic level remains largely unclear. In this study, we applied the all-atom molecular dynamics (MD) method to simulate the interactions of single-transmembrane helical peptide dimers in membrane environments, which has previously been analyzed by single-molecule experiments. The simulations were performed with two peptides (Ala- and Leu-based artificially designed peptides, termed “host peptide”, and the host peptide added with the GXXXG motif, termed “GXXXG peptide”), two membranes (pure-POPC and POPC mixed with 30% cholesterols), and two dimer directions (parallel and antiparallel), consistent with those in the previous experiment. As a result, the MD simulations with parallel dimers reproduced the experimentally observed tendency that introducing cholesterols weakened the interactions in the GXXXG dimer and facilitated those in the host dimer. Our simulation suggested that the host dimer formed hydrogen bonds but the GXXXG dimer did not. However, some discrepancies were also observed between the experiments and simulations. Limitations in the space and time scales of simulations restrict the large-scale undulation and peristaltic motions of the membranes, resulting in differences in lateral pressure profiles. This effect could cause a discrepancy in the rotation angles of helices against the membrane normal.
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spelling pubmed-81539882021-05-27 All-Atom Molecular Dynamics Elucidating Molecular Mechanisms of Single-Transmembrane Model Peptide Dimerization in a Lipid Bilayer Itaya, Hayato Kasahara, Kota Xie, Qilin Yano, Yoshiaki Matsuzaki, Katsumi Takahashi, Takuya ACS Omega [Image: see text] Protein–protein interactions between transmembrane helices are essential elements for membrane protein structures and functions. To understand the effects of peptide sequences and lipid compositions on these interactions, single-molecule experiments using model systems comprising artificial peptides and membranes have been extensively performed. However, their dynamic behavior at the atomic level remains largely unclear. In this study, we applied the all-atom molecular dynamics (MD) method to simulate the interactions of single-transmembrane helical peptide dimers in membrane environments, which has previously been analyzed by single-molecule experiments. The simulations were performed with two peptides (Ala- and Leu-based artificially designed peptides, termed “host peptide”, and the host peptide added with the GXXXG motif, termed “GXXXG peptide”), two membranes (pure-POPC and POPC mixed with 30% cholesterols), and two dimer directions (parallel and antiparallel), consistent with those in the previous experiment. As a result, the MD simulations with parallel dimers reproduced the experimentally observed tendency that introducing cholesterols weakened the interactions in the GXXXG dimer and facilitated those in the host dimer. Our simulation suggested that the host dimer formed hydrogen bonds but the GXXXG dimer did not. However, some discrepancies were also observed between the experiments and simulations. Limitations in the space and time scales of simulations restrict the large-scale undulation and peristaltic motions of the membranes, resulting in differences in lateral pressure profiles. This effect could cause a discrepancy in the rotation angles of helices against the membrane normal. American Chemical Society 2021-04-22 /pmc/articles/PMC8153988/ /pubmed/34056301 http://dx.doi.org/10.1021/acsomega.1c00482 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Itaya, Hayato
Kasahara, Kota
Xie, Qilin
Yano, Yoshiaki
Matsuzaki, Katsumi
Takahashi, Takuya
All-Atom Molecular Dynamics Elucidating Molecular Mechanisms of Single-Transmembrane Model Peptide Dimerization in a Lipid Bilayer
title All-Atom Molecular Dynamics Elucidating Molecular Mechanisms of Single-Transmembrane Model Peptide Dimerization in a Lipid Bilayer
title_full All-Atom Molecular Dynamics Elucidating Molecular Mechanisms of Single-Transmembrane Model Peptide Dimerization in a Lipid Bilayer
title_fullStr All-Atom Molecular Dynamics Elucidating Molecular Mechanisms of Single-Transmembrane Model Peptide Dimerization in a Lipid Bilayer
title_full_unstemmed All-Atom Molecular Dynamics Elucidating Molecular Mechanisms of Single-Transmembrane Model Peptide Dimerization in a Lipid Bilayer
title_short All-Atom Molecular Dynamics Elucidating Molecular Mechanisms of Single-Transmembrane Model Peptide Dimerization in a Lipid Bilayer
title_sort all-atom molecular dynamics elucidating molecular mechanisms of single-transmembrane model peptide dimerization in a lipid bilayer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153988/
https://www.ncbi.nlm.nih.gov/pubmed/34056301
http://dx.doi.org/10.1021/acsomega.1c00482
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