Insertases scramble lipids: Molecular simulations  of MTCH2

J 2024

Insertases scramble lipids: Molecular simulations of MTCH2

BARTOŠ, Ladislav; Anant K. MENON a Robert VÁCHA

Základní údaje

Originální název

Insertases scramble lipids: Molecular simulations of MTCH2

Autoři

BARTOŠ, Ladislav ; Anant K. MENON a Robert VÁCHA

Vydání

Structure, ENGLAND, CELL PRESS, 2024, 0969-2126

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.300

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/24:00135778

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1016/j.str.2024.01.012

UT WoS

001224291300001

EID Scopus

2-s2.0-85187561128

Klíčová slova anglicky

flip-flop rate; free energy barrier; hydrophilic groove; insertase; membrane defect; molecular dynamics; scramblase

Štítky

NIVB_CEITEC, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 3. 6. 2025 12:30, Mgr. Eva Dubská

Anotace

V originále

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.

Návaznosti

LX22NPO5103, projekt VaV

Název: Národní institut virologie a bakteriologie (Akronym: NIVB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní institut virologie a bakteriologie, 5.1 EXCELES

101001470, interní kód MU

Název: Peptide Killers of Bacteria (Akronym: PeptideKillers)

Investor: Evropská unie, Peptide Killers of Bacteria, ERC (Excellent Science)

90254, velká výzkumná infrastruktura

Název: e-INFRA CZ II

Přiložené soubory

Insertases_scramble_lipids_Molecular_simulations.pdf

Citovat

BARTOŠ, Ladislav; Anant K. MENON a Robert VÁCHA. Insertases scramble lipids: Molecular simulations of MTCH2. Structure. ENGLAND: CELL PRESS, 2024, roč. 32, č. 4, s. 1-11. ISSN 0969-2126. Dostupné z: https://doi.org/10.1016/j.str.2024.01.012.

@article{2392637,
   author = {Bartoš, Ladislav and Menon, Anant K. and Vácha, Robert},
   article_location = {ENGLAND},
   article_number = {4},
   doi = {https://doi.org/10.1016/j.str.2024.01.012},
   keywords = {flip-flop rate; free energy barrier; hydrophilic groove; insertase; membrane defect; molecular dynamics; scramblase},
   language = {eng},
   issn = {0969-2126},
   journal = {Structure},
   title = {Insertases scramble lipids: Molecular simulations of MTCH2},
   url = {https://www.sciencedirect.com/science/article/pii/S0969212624000364?via%3Dihub},
   volume = {32},
   year = {2024}
}

TY  - JOUR
ID  - 2392637
AU  - Bartoš, Ladislav - Menon, Anant K. - Vácha, Robert
PY  - 2024
TI  - Insertases scramble lipids: Molecular simulations of MTCH2
JF  - Structure
VL  - 32
IS  - 4
SP  - 1-11
EP  - 1-11
PB  - CELL PRESS
SN  - 09692126
KW  - flip-flop rate
KW  - free energy barrier
KW  - hydrophilic groove
KW  - insertase
KW  - membrane defect
KW  - molecular dynamics
KW  - scramblase
UR  - https://www.sciencedirect.com/science/article/pii/S0969212624000364?via%3Dihub
N2  - 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.
ER  -

BARTOŠ, Ladislav; Anant K. MENON a Robert VÁCHA. Insertases scramble lipids: Molecular simulations of MTCH2. \textit{Structure}. ENGLAND: CELL PRESS, 2024, roč.~32, č.~4, s.~1-11. ISSN~0969-2126. Dostupné z: https://doi.org/10.1016/j.str.2024.01.012.

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