Insertases scramble lipids: Molecular simulations of MTCH2.
| Autor: | Bartoš L; CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic., Menon AK; Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA., Vácha R; CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic; Department of Condensed Matter Physics, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic. Electronic address: robert.vacha@muni.cz. |
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| Jazyk: | angličtina |
| Zdroj: | Structure (London, England : 1993) [Structure] 2024 Apr 04; Vol. 32 (4), pp. 505-510.e4. Date of Electronic Publication: 2024 Feb 19. |
| DOI: | 10.1016/j.str.2024.01.012 |
| Abstrakt: | 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 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 voltage-dependent anion channel (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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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