期刊
ACS NANO
卷 14, 期 12, 页码 16919-16928出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c05960
关键词
membrane curvature; phosphatidylinositol 4, 5-bisphosphate; molecular dynamics; coarse-grained simulations; epsin N-terminal homology domain
类别
资金
- Engineering and Physical Sciences Research Council (EPSRC) Centre for Doctoral Training in the Advanced Characterisation of Materials [EP/L015277/1]
- ERC Seventh Framework Programme Consolidator Grant Naturale CG [616417]
- Wellcome Trust Senior Investigator Award [098411/Z/12/Z]
- Wellcome Trust [208361/Z/17/Z]
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/R00126X/1]
- EPSRC [EP/R004722/1]
- BBSRC [BB/R00126X/1] Funding Source: UKRI
- EPSRC [EP/R004722/1] Funding Source: UKRI
- MRC [MC_PC_14131] Funding Source: UKRI
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 alpha helix via another structural region we have denoted as H3, re-emphasizing the critical relationship between nanoscale membrane curvature and protein function.
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