Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling
| Autor: | Marta Sawicka, Carolina Alvadia, Monique S. Straub, Raimund Dutzler |
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| Přispěvatelé: | University of Zurich, Dutzler, Raimund |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Phospholipid scramblase Structural Biology and Molecular Biophysics Lipid Bilayers 0302 clinical medicine 2400 General Immunology and Microbiology Biology (General) Lipid bilayer Caspase cryo-electron microscpy 0303 health sciences biology Chemistry Caspase 3 General Neuroscience apoptosis 2800 General Neuroscience General Medicine synthetic nanobody Cell biology Caspases Medicine lipid scramblase Hydrophobic and Hydrophilic Interactions Intracellular Research Article Human QH301-705.5 Science 610 Medicine & health Phosphatidylserines General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 1300 General Biochemistry Genetics and Molecular Biology 10019 Department of Biochemistry Animals Humans 030304 developmental biology Membranes General Immunology and Microbiology Cell Membrane Cryoelectron Microscopy Membrane Proteins Rats HEK293 Cells Structural biology Membrane protein Cytoplasm biology.protein Rat 570 Life sciences Apoptosis Regulatory Proteins 030217 neurology & neurosurgery Alpha helix |
| Zdroj: | eLife eLife, Vol 10 (2021) |
| Popis: | The exposure of the negatively charged lipid phosphatidylserine on the cell surface, catalyzed by lipid scramblases, is an important signal for the clearance of apoptotic cells by macrophages. The protein XKR9 is a member of a conserved family that has been associated with apoptotic lipid scrambling. Here, we describe structures of full-length and caspase-treated XKR9 from Rattus norvegicus in complex with a synthetic nanobody determined by cryo-electron microscopy. The 43 kDa monomeric membrane protein can be divided into two structurally related repeats, each containing four membrane-spanning segments and a helix that is partly inserted into the lipid bilayer. In the full-length protein, the C-terminus interacts with a hydrophobic pocket located at the intracellular side acting as an inhibitor of protein function. Cleavage by caspase-3 at a specific site releases 16 residues of the C-terminus, thus making the pocket accessible to the cytoplasm. Collectively, the work has revealed the unknown architecture of the XKR family and has provided initial insight into its activation by caspases. |
| Databáze: | OpenAIRE |
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