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Dissecting peripheral protein-membrane interfaces

Peripheral membrane proteins (PMPs) include a wide variety of proteins that have in common to bind transiently to the chemically complex interfacial region of membranes through their interfacial binding site (IBS). In contrast to protein-protein or protein-DNA/RNA interfaces, peripheral protein-memb...

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Autores principales: Tubiana, Thibault, Sillitoe, Ian, Orengo, Christine, Reuter, Nathalie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797079/
https://www.ncbi.nlm.nih.gov/pubmed/36516231
http://dx.doi.org/10.1371/journal.pcbi.1010346
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author Tubiana, Thibault
Sillitoe, Ian
Orengo, Christine
Reuter, Nathalie
author_facet Tubiana, Thibault
Sillitoe, Ian
Orengo, Christine
Reuter, Nathalie
author_sort Tubiana, Thibault
collection PubMed
description Peripheral membrane proteins (PMPs) include a wide variety of proteins that have in common to bind transiently to the chemically complex interfacial region of membranes through their interfacial binding site (IBS). In contrast to protein-protein or protein-DNA/RNA interfaces, peripheral protein-membrane interfaces are poorly characterized. We collected a dataset of PMP domains representative of the variety of PMP functions: membrane-targeting domains (Annexin, C1, C2, discoidin C2, PH, PX), enzymes (PLA, PLC/D) and lipid-transfer proteins (START). The dataset contains 1328 experimental structures and 1194 AphaFold models. We mapped the amino acid composition and structural patterns of the IBS of each protein in this dataset, and evaluated which were more likely to be found at the IBS compared to the rest of the domains’ accessible surface. In agreement with earlier work we find that about two thirds of the PMPs in the dataset have protruding hydrophobes (Leu, Ile, Phe, Tyr, Trp and Met) at their IBS. The three aromatic amino acids Trp, Tyr and Phe are a hallmark of PMPs IBS regardless of whether they protrude on loops or not. This is also the case for lysines but not arginines suggesting that, unlike for Arg-rich membrane-active peptides, the less membrane-disruptive lysine is preferred in PMPs. Another striking observation was the over-representation of glycines at the IBS of PMPs compared to the rest of their surface, possibly procuring IBS loops a much-needed flexibility to insert in-between membrane lipids. The analysis of the 9 superfamilies revealed amino acid distribution patterns in agreement with their known functions and membrane-binding mechanisms. Besides revealing novel amino acids patterns at protein-membrane interfaces, our work contributes a new PMP dataset and an analysis pipeline that can be further built upon for future studies of PMPs properties, or for developing PMPs prediction tools using for example, machine learning approaches.
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spelling pubmed-97970792022-12-29 Dissecting peripheral protein-membrane interfaces Tubiana, Thibault Sillitoe, Ian Orengo, Christine Reuter, Nathalie PLoS Comput Biol Research Article Peripheral membrane proteins (PMPs) include a wide variety of proteins that have in common to bind transiently to the chemically complex interfacial region of membranes through their interfacial binding site (IBS). In contrast to protein-protein or protein-DNA/RNA interfaces, peripheral protein-membrane interfaces are poorly characterized. We collected a dataset of PMP domains representative of the variety of PMP functions: membrane-targeting domains (Annexin, C1, C2, discoidin C2, PH, PX), enzymes (PLA, PLC/D) and lipid-transfer proteins (START). The dataset contains 1328 experimental structures and 1194 AphaFold models. We mapped the amino acid composition and structural patterns of the IBS of each protein in this dataset, and evaluated which were more likely to be found at the IBS compared to the rest of the domains’ accessible surface. In agreement with earlier work we find that about two thirds of the PMPs in the dataset have protruding hydrophobes (Leu, Ile, Phe, Tyr, Trp and Met) at their IBS. The three aromatic amino acids Trp, Tyr and Phe are a hallmark of PMPs IBS regardless of whether they protrude on loops or not. This is also the case for lysines but not arginines suggesting that, unlike for Arg-rich membrane-active peptides, the less membrane-disruptive lysine is preferred in PMPs. Another striking observation was the over-representation of glycines at the IBS of PMPs compared to the rest of their surface, possibly procuring IBS loops a much-needed flexibility to insert in-between membrane lipids. The analysis of the 9 superfamilies revealed amino acid distribution patterns in agreement with their known functions and membrane-binding mechanisms. Besides revealing novel amino acids patterns at protein-membrane interfaces, our work contributes a new PMP dataset and an analysis pipeline that can be further built upon for future studies of PMPs properties, or for developing PMPs prediction tools using for example, machine learning approaches. Public Library of Science 2022-12-14 /pmc/articles/PMC9797079/ /pubmed/36516231 http://dx.doi.org/10.1371/journal.pcbi.1010346 Text en © 2022 Tubiana et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Tubiana, Thibault
Sillitoe, Ian
Orengo, Christine
Reuter, Nathalie
Dissecting peripheral protein-membrane interfaces
title Dissecting peripheral protein-membrane interfaces
title_full Dissecting peripheral protein-membrane interfaces
title_fullStr Dissecting peripheral protein-membrane interfaces
title_full_unstemmed Dissecting peripheral protein-membrane interfaces
title_short Dissecting peripheral protein-membrane interfaces
title_sort dissecting peripheral protein-membrane interfaces
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797079/
https://www.ncbi.nlm.nih.gov/pubmed/36516231
http://dx.doi.org/10.1371/journal.pcbi.1010346
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