The Role of Protein–Lipid Interactions in Priming the Bacterial Translocon

Protein–lipid interactions demonstrate important regulatory roles in the function of membrane proteins. Nevertheless, due to the semi-liquid nature and heterogeneity of biological membranes, and dissecting the details of such interactions at high resolutions continues to pose a major challenge to ex...

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Main Authors: Matt Sinclair, Emad Tajkhorshid
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Membranes
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Online Access:https://www.mdpi.com/2077-0375/14/12/249
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author Matt Sinclair
Emad Tajkhorshid
author_facet Matt Sinclair
Emad Tajkhorshid
author_sort Matt Sinclair
collection DOAJ
description Protein–lipid interactions demonstrate important regulatory roles in the function of membrane proteins. Nevertheless, due to the semi-liquid nature and heterogeneity of biological membranes, and dissecting the details of such interactions at high resolutions continues to pose a major challenge to experimental biophysical techniques. Computational techniques such as molecular dynamics (MD) offer an alternative approach with both temporally and spatially high resolutions. Here, we present an extensive series of MD simulations focused on the inner membrane protein YidC (PDB: 6AL2) from <i>Escherichia coli</i>, a key insertase responsible for the integration and folding of membrane proteins. Notably, we observed rare lipid fenestration events, where lipids fully penetrate the vestibule of YidC, providing new insights into the lipid-mediated regulation of protein insertion mechanisms. Our findings highlight the direct involvement of lipids in modulating the greasy slide of YidC and suggest that lipids enhance the local flexibility of the C1 domain, which is crucial for recruiting substrate peptides. These results contribute to a deeper understanding of how protein–lipid interactions facilitate the functional dynamics of membrane protein insertases, with implications for broader studies of membrane protein biology.
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spelling doaj-art-e55cbf71c9f24de9b3f71c3447c67b102024-12-27T14:39:19ZengMDPI AGMembranes2077-03752024-11-01141224910.3390/membranes14120249The Role of Protein–Lipid Interactions in Priming the Bacterial TransloconMatt Sinclair0Emad Tajkhorshid1Department of Biochemistry, University of Illinois Urbana, Champaign, IL 61801, USADepartment of Biochemistry, University of Illinois Urbana, Champaign, IL 61801, USAProtein–lipid interactions demonstrate important regulatory roles in the function of membrane proteins. Nevertheless, due to the semi-liquid nature and heterogeneity of biological membranes, and dissecting the details of such interactions at high resolutions continues to pose a major challenge to experimental biophysical techniques. Computational techniques such as molecular dynamics (MD) offer an alternative approach with both temporally and spatially high resolutions. Here, we present an extensive series of MD simulations focused on the inner membrane protein YidC (PDB: 6AL2) from <i>Escherichia coli</i>, a key insertase responsible for the integration and folding of membrane proteins. Notably, we observed rare lipid fenestration events, where lipids fully penetrate the vestibule of YidC, providing new insights into the lipid-mediated regulation of protein insertion mechanisms. Our findings highlight the direct involvement of lipids in modulating the greasy slide of YidC and suggest that lipids enhance the local flexibility of the C1 domain, which is crucial for recruiting substrate peptides. These results contribute to a deeper understanding of how protein–lipid interactions facilitate the functional dynamics of membrane protein insertases, with implications for broader studies of membrane protein biology.https://www.mdpi.com/2077-0375/14/12/249molecular dynamicstranslocaseinsertaseprotein–lipid interactions
spellingShingle Matt Sinclair
Emad Tajkhorshid
The Role of Protein–Lipid Interactions in Priming the Bacterial Translocon
Membranes
molecular dynamics
translocase
insertase
protein–lipid interactions
title The Role of Protein–Lipid Interactions in Priming the Bacterial Translocon
title_full The Role of Protein–Lipid Interactions in Priming the Bacterial Translocon
title_fullStr The Role of Protein–Lipid Interactions in Priming the Bacterial Translocon
title_full_unstemmed The Role of Protein–Lipid Interactions in Priming the Bacterial Translocon
title_short The Role of Protein–Lipid Interactions in Priming the Bacterial Translocon
title_sort role of protein lipid interactions in priming the bacterial translocon
topic molecular dynamics
translocase
insertase
protein–lipid interactions
url https://www.mdpi.com/2077-0375/14/12/249
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