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Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298096/ https://www.ncbi.nlm.nih.gov/pubmed/34263724 http://dx.doi.org/10.7554/eLife.69800 |
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author | Straub, Monique S Alvadia, Carolina Sawicka, Marta Dutzler, Raimund |
author_facet | Straub, Monique S Alvadia, Carolina Sawicka, Marta Dutzler, Raimund |
author_sort | Straub, Monique S |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8298096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-82980962021-07-23 Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling Straub, Monique S Alvadia, Carolina Sawicka, Marta Dutzler, Raimund eLife Structural Biology and Molecular Biophysics 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. eLife Sciences Publications, Ltd 2021-07-15 /pmc/articles/PMC8298096/ /pubmed/34263724 http://dx.doi.org/10.7554/eLife.69800 Text en © 2021, Straub et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Structural Biology and Molecular Biophysics Straub, Monique S Alvadia, Carolina Sawicka, Marta Dutzler, Raimund Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling |
title | Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling |
title_full | Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling |
title_fullStr | Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling |
title_full_unstemmed | Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling |
title_short | Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling |
title_sort | cryo-em structures of the caspase-activated protein xkr9 involved in apoptotic lipid scrambling |
topic | Structural Biology and Molecular Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298096/ https://www.ncbi.nlm.nih.gov/pubmed/34263724 http://dx.doi.org/10.7554/eLife.69800 |
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