| Autor: |
Edward N. Schmidt, Dimitra Lamprinaki, Kelli A. McCord, Maju Joe, Mirat Sojitra, Ayk Waldow, Jasmine Nguyen, John Monyror, Elena N. Kitova, Fahima Mozaneh, Xue Yan Guo, Jaesoo Jung, Jhon R. Enterina, Gour C. Daskhan, Ling Han, Amanda R. Krysler, Christopher R. Cromwell, Basil P. Hubbard, Lori J. West, Marianne Kulka, Simonetta Sipione, John S. Klassen, Ratmir Derda, Todd L. Lowary, Lara K. Mahal, Meghan R. Riddell, Matthew S. Macauley |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-17 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-38030-6 |
| Popis: |
Abstract Immunomodulatory Siglecs are controlled by their glycoprotein and glycolipid ligands. Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer, missing the complex behaviors of glycolipids in a membrane. Through optimizing a liposomal formulation to dissect Siglec–glycolipid interactions, it is shown that Siglec-6 can recognize glycolipids independent of its canonical binding pocket, suggesting that Siglec-6 possesses a secondary binding pocket tailored for recognizing glycolipids in a bilayer. A panel of synthetic neoglycolipids is used to probe the specificity of this glycolipid binding pocket on Siglec-6, leading to the development of a neoglycolipid with higher avidity for Siglec-6 compared to natural glycolipids. This neoglycolipid facilitates the delivery of liposomes to Siglec-6 on human mast cells, memory B-cells and placental syncytiotrophoblasts. A physiological relevance for glycolipid recognition by Siglec-6 is revealed for the binding and internalization of extracellular vesicles. These results demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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