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Cryo-EM structure of human XKR8-basigin complex in lipid nanodisc
Structural highlights
FunctionBASI_HUMAN Plays an important role in targeting the monocarboxylate transporters SLC16A1, SLC16A3 and SLC16A8 to the plasma membrane. Plays pivotal roles in spermatogenesis, embryo implantation, neural network formation and tumor progression. Stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPS). Seems to be a receptor for oligomannosidic glycans. In vitro, promotes outgrowth of astrocytic processes.[1] Publication Abstract from PubMedXK-related 8 (XKR8), in complex with the transmembrane glycoprotein basigin, functions as a phospholipid scramblase activated by the caspase-mediated cleavage or phosphorylation of its C-terminal tail. It carries a putative phospholipid translocation path of multiple hydrophobic and charged residues in the transmembrane region. It also has a crucial tryptophan at the exoplasmic end of the path that regulates its scrambling activity. We herein investigated the tertiary structure of the human XKR8-basigin complex embedded in lipid nanodiscs at an overall resolution of 3.66 A. We found that the C-terminal tail engaged in intricate polar and van der Waals interactions with a groove at the cytoplasmic surface of XKR8. These interactions maintained the inactive state of XKR8. Point mutations to disrupt these interactions strongly enhanced the scrambling activity of XKR8, suggesting that the activation of XKR8 is mediated by releasing the C-terminal tail from the cytoplasmic groove. We speculate that the cytoplasmic tail region of XKR8 functions as a plug to prevent the scrambling of phospholipids. The role of the C-terminal tail region as a plug to regulate XKR8 lipid scramblase.,Sakuragi T, Kanai R, Otani M, Kikkawa M, Toyoshima C, Nagata S J Biol Chem. 2024 Mar;300(3):105755. doi: 10.1016/j.jbc.2024.105755. Epub 2024 , Feb 15. PMID:38364890[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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