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Insertases Scramble Lipids: Molecular Simulations of MTCH2
Scramblases play a pivotal role in facilitating bidirectional lipid transport across cell membranes, thereby influencing lipid metabolism, membrane homeostasis, and cellular signaling. MTCH2, a mitochondrial outer membrane protein insertase, has a membrane-spanning hydrophilic groove resembling thos...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462046/ https://www.ncbi.nlm.nih.gov/pubmed/37645813 http://dx.doi.org/10.1101/2023.08.14.553169 |
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author | Bartoš, Ladislav Menon, Anant K. Vácha, Robert |
author_facet | Bartoš, Ladislav Menon, Anant K. Vácha, Robert |
author_sort | Bartoš, Ladislav |
collection | PubMed |
description | Scramblases play a pivotal role in facilitating bidirectional lipid transport across cell membranes, thereby influencing lipid metabolism, membrane homeostasis, and cellular signaling. MTCH2, a mitochondrial outer membrane protein insertase, has a membrane-spanning hydrophilic groove resembling those that form the lipid transit pathway in known scramblases. Employing both coarse-grained and atomistic molecular dynamics simulations, we now show that MTCH2 significantly reduces the free energy barrier for lipid movement along the groove and therefore can indeed function as a scramblase. Notably, the scrambling rate of MTCH2 in silico is similar to that of VDAC, a recently discovered scramblase of the outer mitochondrial membrane, suggesting a potential complementary physiological role for these mitochondrial proteins. Finally, our findings suggest that other insertases which possess a hydrophilic path across the membrane like MTCH2, can also function as scramblases. |
format | Online Article Text |
id | pubmed-10462046 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-104620462023-08-29 Insertases Scramble Lipids: Molecular Simulations of MTCH2 Bartoš, Ladislav Menon, Anant K. Vácha, Robert bioRxiv Article Scramblases play a pivotal role in facilitating bidirectional lipid transport across cell membranes, thereby influencing lipid metabolism, membrane homeostasis, and cellular signaling. MTCH2, a mitochondrial outer membrane protein insertase, has a membrane-spanning hydrophilic groove resembling those that form the lipid transit pathway in known scramblases. Employing both coarse-grained and atomistic molecular dynamics simulations, we now show that MTCH2 significantly reduces the free energy barrier for lipid movement along the groove and therefore can indeed function as a scramblase. Notably, the scrambling rate of MTCH2 in silico is similar to that of VDAC, a recently discovered scramblase of the outer mitochondrial membrane, suggesting a potential complementary physiological role for these mitochondrial proteins. Finally, our findings suggest that other insertases which possess a hydrophilic path across the membrane like MTCH2, can also function as scramblases. Cold Spring Harbor Laboratory 2023-08-14 /pmc/articles/PMC10462046/ /pubmed/37645813 http://dx.doi.org/10.1101/2023.08.14.553169 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Bartoš, Ladislav Menon, Anant K. Vácha, Robert Insertases Scramble Lipids: Molecular Simulations of MTCH2 |
title | Insertases Scramble Lipids: Molecular Simulations of MTCH2 |
title_full | Insertases Scramble Lipids: Molecular Simulations of MTCH2 |
title_fullStr | Insertases Scramble Lipids: Molecular Simulations of MTCH2 |
title_full_unstemmed | Insertases Scramble Lipids: Molecular Simulations of MTCH2 |
title_short | Insertases Scramble Lipids: Molecular Simulations of MTCH2 |
title_sort | insertases scramble lipids: molecular simulations of mtch2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462046/ https://www.ncbi.nlm.nih.gov/pubmed/37645813 http://dx.doi.org/10.1101/2023.08.14.553169 |
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