mPPases create a conserved anionic membrane fingerprint as identified via multi-scale simulations.
Membrane-integral pyrophosphatases (mPPases) are membrane-bound enzymes responsible for hydrolysing inorganic pyrophosphate and translocating a cation across the membrane. Their function is essential for the infectivity of clinically relevant protozoan parasites and plant maturation. Recent developm...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-10-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1010578 |
| _version_ | 1811257309602512896 |
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| author | Alexandra O M Holmes Adrian Goldman Antreas C Kalli |
| author_facet | Alexandra O M Holmes Adrian Goldman Antreas C Kalli |
| author_sort | Alexandra O M Holmes |
| collection | DOAJ |
| description | Membrane-integral pyrophosphatases (mPPases) are membrane-bound enzymes responsible for hydrolysing inorganic pyrophosphate and translocating a cation across the membrane. Their function is essential for the infectivity of clinically relevant protozoan parasites and plant maturation. Recent developments have indicated that their mechanism is more complicated than previously thought and that the membrane environment may be important for their function. In this work, we use multiscale molecular dynamics simulations to demonstrate for the first time that mPPases form specific anionic lipid interactions at 4 sites at the distal and interfacial regions of the protein. These interactions are conserved in simulations of the mPPases from Thermotoga maritima, Vigna radiata and Clostridium leptum and characterised by interactions with positive residues on helices 1, 2, 3 and 4 for the distal site, or 9, 10, 13 and 14 for the interfacial site. Due to the importance of these helices in protein stability and function, these lipid interactions may play a crucial role in the mPPase mechanism and enable future structural and functional studies. |
| first_indexed | 2024-04-12T17:54:25Z |
| format | Article |
| id | doaj.art-2b179b09f8644df08a9ca16c37a4c260 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-12T17:54:25Z |
| publishDate | 2022-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-2b179b09f8644df08a9ca16c37a4c2602022-12-22T03:22:23ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582022-10-011810e101057810.1371/journal.pcbi.1010578mPPases create a conserved anionic membrane fingerprint as identified via multi-scale simulations.Alexandra O M HolmesAdrian GoldmanAntreas C KalliMembrane-integral pyrophosphatases (mPPases) are membrane-bound enzymes responsible for hydrolysing inorganic pyrophosphate and translocating a cation across the membrane. Their function is essential for the infectivity of clinically relevant protozoan parasites and plant maturation. Recent developments have indicated that their mechanism is more complicated than previously thought and that the membrane environment may be important for their function. In this work, we use multiscale molecular dynamics simulations to demonstrate for the first time that mPPases form specific anionic lipid interactions at 4 sites at the distal and interfacial regions of the protein. These interactions are conserved in simulations of the mPPases from Thermotoga maritima, Vigna radiata and Clostridium leptum and characterised by interactions with positive residues on helices 1, 2, 3 and 4 for the distal site, or 9, 10, 13 and 14 for the interfacial site. Due to the importance of these helices in protein stability and function, these lipid interactions may play a crucial role in the mPPase mechanism and enable future structural and functional studies.https://doi.org/10.1371/journal.pcbi.1010578 |
| spellingShingle | Alexandra O M Holmes Adrian Goldman Antreas C Kalli mPPases create a conserved anionic membrane fingerprint as identified via multi-scale simulations. PLoS Computational Biology |
| title | mPPases create a conserved anionic membrane fingerprint as identified via multi-scale simulations. |
| title_full | mPPases create a conserved anionic membrane fingerprint as identified via multi-scale simulations. |
| title_fullStr | mPPases create a conserved anionic membrane fingerprint as identified via multi-scale simulations. |
| title_full_unstemmed | mPPases create a conserved anionic membrane fingerprint as identified via multi-scale simulations. |
| title_short | mPPases create a conserved anionic membrane fingerprint as identified via multi-scale simulations. |
| title_sort | mppases create a conserved anionic membrane fingerprint as identified via multi scale simulations |
| url | https://doi.org/10.1371/journal.pcbi.1010578 |
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