Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix
© 2020 American Chemical Society. Nanoscale membrane curvature is a common feature in cell biology required for functions such as endocytosis, exocytosis and cell migration. These processes require the cytoskeleton to exert forces on the membrane to deform it. Cytosolic proteins contain specific mot...
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| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2022
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| Online Access: | https://hdl.handle.net/1721.1/142467 |
| _version_ | 1826215602509840384 |
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| author | Belessiotis-Richards, Alexis Higgins, Stuart G Sansom, Mark SP Alexander-Katz, Alfredo Stevens, Molly M |
| author2 | Massachusetts Institute of Technology. Department of Materials Science and Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Materials Science and Engineering Belessiotis-Richards, Alexis Higgins, Stuart G Sansom, Mark SP Alexander-Katz, Alfredo Stevens, Molly M |
| author_sort | Belessiotis-Richards, Alexis |
| collection | MIT |
| description | © 2020 American Chemical Society. Nanoscale membrane curvature is a common feature in cell biology required for functions such as endocytosis, exocytosis and cell migration. These processes require the cytoskeleton to exert forces on the membrane to deform it. Cytosolic proteins contain specific motifs which bind to the membrane, connecting it to the internal cytoskeletal machinery. These motifs often bind charged phosphatidylinositol phosphate lipids present in the cell membrane which play significant roles in signaling. These lipids are important for membrane deforming processes, such as endocytosis, but much remains unknown about their role in the sensing of membrane nanocurvature by protein domains. Using coarse-grained molecular dynamics simulations, we investigated the interaction of a model curvature active protein domain, the epsin N-terminal homology domain (ENTH), with curved lipid membranes. The combination of anionic lipids (phosphatidylinositol 4,5-bisphosphate and phosphatidylserine) within the membrane, protein backbone flexibility, and structural changes within the domain were found to affect the domain's ability to sense, bind, and localize with nanoscale precision at curved membrane regions. The findings suggest that the ENTH domain can sense membrane curvature without the presence of its terminal amphipathic α helix via another structural region we have denoted as H3, re-emphasizing the critical relationship between nanoscale membrane curvature and protein function. |
| first_indexed | 2024-09-23T16:36:30Z |
| format | Article |
| id | mit-1721.1/142467 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:36:30Z |
| publishDate | 2022 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1424672023-01-11T21:39:02Z Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix Belessiotis-Richards, Alexis Higgins, Stuart G Sansom, Mark SP Alexander-Katz, Alfredo Stevens, Molly M Massachusetts Institute of Technology. Department of Materials Science and Engineering © 2020 American Chemical Society. Nanoscale membrane curvature is a common feature in cell biology required for functions such as endocytosis, exocytosis and cell migration. These processes require the cytoskeleton to exert forces on the membrane to deform it. Cytosolic proteins contain specific motifs which bind to the membrane, connecting it to the internal cytoskeletal machinery. These motifs often bind charged phosphatidylinositol phosphate lipids present in the cell membrane which play significant roles in signaling. These lipids are important for membrane deforming processes, such as endocytosis, but much remains unknown about their role in the sensing of membrane nanocurvature by protein domains. Using coarse-grained molecular dynamics simulations, we investigated the interaction of a model curvature active protein domain, the epsin N-terminal homology domain (ENTH), with curved lipid membranes. The combination of anionic lipids (phosphatidylinositol 4,5-bisphosphate and phosphatidylserine) within the membrane, protein backbone flexibility, and structural changes within the domain were found to affect the domain's ability to sense, bind, and localize with nanoscale precision at curved membrane regions. The findings suggest that the ENTH domain can sense membrane curvature without the presence of its terminal amphipathic α helix via another structural region we have denoted as H3, re-emphasizing the critical relationship between nanoscale membrane curvature and protein function. 2022-05-11T15:08:09Z 2022-05-11T15:08:09Z 2020 2022-05-11T14:58:22Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/142467 Belessiotis-Richards, Alexis, Higgins, Stuart G, Sansom, Mark SP, Alexander-Katz, Alfredo and Stevens, Molly M. 2020. "Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix." ACS Nano, 14 (12). en 10.1021/ACSNANO.0C05960 ACS Nano Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0 application/pdf American Chemical Society (ACS) American Chemical Society |
| spellingShingle | Belessiotis-Richards, Alexis Higgins, Stuart G Sansom, Mark SP Alexander-Katz, Alfredo Stevens, Molly M Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix |
| title | Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix |
| title_full | Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix |
| title_fullStr | Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix |
| title_full_unstemmed | Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix |
| title_short | Coarse-Grained Simulations Suggest the Epsin N-Terminal Homology Domain Can Sense Membrane Curvature without Its Terminal Amphipathic Helix |
| title_sort | coarse grained simulations suggest the epsin n terminal homology domain can sense membrane curvature without its terminal amphipathic helix |
| url | https://hdl.handle.net/1721.1/142467 |
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