Binding of DEP domain to phospholipid membranes: More than just electrostatics
| Autoři | |
|---|---|
| Rok publikování | 2022 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Biochimica et Biophysica Acta (BBA) - Biomembranes |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://doi.org/10.1016/j.bbamem.2022.183983 |
| Doi | http://dx.doi.org/10.1016/j.bbamem.2022.183983 |
| Klíčová slova | DVL protein; DEP domain; Lipid membrane; Molecular dynamics; Flow cytometry; QCM-D; Lipid preference; Phosphatidylserine; Phosphatidic acid; Phosphatidylinositol |
| Přiložené soubory | |
| Popis | Over the past decades an extensive effort has been made to provide a more comprehensive understanding of Wnt signaling, yet many regulatory and structural aspects remain elusive. Among these, the ability of Dishevelled (DVL) protein to relocalize at the plasma membrane is a crucial step in the activation of all Wnt pathways. The membrane binding of DVL was suggested to be mediated by the preferential interaction of its C-terminal DEP domain with phosphatidic acid (PA). However, due to the scarcity and fast turnover of PA, we investigated the role on the membrane association of other more abundant phospholipids. The combined results from computational simulations and experimental measurements with various model phospholipid membranes, demonstrate that the membrane binding of DEP/DVL constructs is governed by the concerted action of generic electrostatics and finely-tuned intermolecular interactions with individual lipid species. In particular, while we confirmed the strong preference for PA lipid, we also observed a weak but non-negligible affinity for phosphatidylserine, the most abundant anionic phospholipid in the plasma membrane, and phosphatidylinositol 4,5-bisphosphate. The obtained molecular insight into DEP-membrane interaction helps to elucidate the relation between changes in the local membrane composition and the spatiotemporal localization of DVL and, possibly, other DEP-containing proteins. |
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