Structural insights into the aPKC regulatory switch mechanism of the human cell polarity protein lethal giant larvae 2
| Autor: | Jingzhi Li, Ivan S. Ufimtsev, Aruna Ayer, Lior Almagor, William I. Weis |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
inorganic chemicals
Models Molecular Phosphatidylinositol 4 5-Diphosphate Conformational change Polarity (physics) macromolecular substances environment and public health 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell polarity Humans Phosphatidylinositol Phosphorylation Protein Kinase C 030304 developmental biology Epithelial polarity 0303 health sciences Multidisciplinary Cell Polarity Apical membrane In vitro Cell biology enzymes and coenzymes (carbohydrates) Cytoskeletal Proteins chemistry PNAS Plus bacteria 030217 neurology & neurosurgery |
| Popis: | Metazoan cell polarity is controlled by a set of highly conserved proteins. Lethal giant larvae (Lgl) functions in apical-basal polarity through phosphorylation-dependent interactions with several other proteins as well as the plasma membrane. Phosphorylation of Lgl by atypical protein kinase C (aPKC), a component of the partitioning-defective (Par) complex in epithelial cells, excludes Lgl from the apical membrane, a crucial step in the establishment of epithelial cell polarity. We present the crystal structures of human Lgl2 in both its unphosphorylated and aPKC-phosphorylated states. Lgl2 adopts a double β-propeller structure that is unchanged by aPKC phosphorylation of an unstructured loop in its second β-propeller, ruling out models of phosphorylation-dependent conformational change. We demonstrate that phosphorylation controls the direct binding of purified Lgl2 to negative phospholipids in vitro. We also show that a coil–helix transition of this region that is promoted by phosphatidylinositol 4,5-bisphosphate (PIP 2 ) is also phosphorylation-dependent, implying a highly effective phosphorylative switch for membrane association. |
| Databáze: | OpenAIRE |
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