1.A.79.1.2
The human SIDT1 protein (Duxbury et al. 2005; Pratt et al. 2012). This protein as well as SidT2 may be cholesterol transporters (Méndez-Acevedo et al. 2017), although they are annotated as RNA transporters, in accordance with several earlier publications. Morreover, SIDT1 localizes to endolysosomes and mediates double-stranded RNA transport into the cytoplasm (Nguyen et al. 2019). SIDT1 plays a key role in type I IFN responses to nucleic acids in plasmacytoid dendritic cells and mediates the pathogenesis of an imiquimod-induced psoriasis model (Morell et al. 2022). SIDT1-dependent absorption in the stomach mediates host uptake of dietary and orally administered microRNAs (Chen et al. 2021). The structure of the human systemic RNAi defective transmembrane protein 1 (hSIDT1) has revealed the conformational flexibility of its lipid binding domain (Navratna et al. 2023).  Several subgroups of the family have been identified as cognate endopeptidases for four protein-sorting signals processed by a previously unknown machinery. Sorting signals with newly identified processing enzymes include MYXO-CTERM and three novel ones (Haft 2024).  N-glycosylation is required for its functional role in SIDT1-mediated RNA uptake (Yang et al. 2024). The structure of recombinant human SIDT1 has been solved revealing that the extra-cytosolic domain of hSIDT1 adopts a double jelly roll fold, and the transmembrane domain exists as two modules - a flexible lipid binding domain and a rigid transmembrane domain core. These structural analyses provide insights into the inherent conformational dynamics within the lipid binding domain in ChUP family members (Navratna et al. 2024).  Cryo-EM analysis revealed that human SID-1 transmembrane family member 1 dynamics underlie lipid hydrolytic activity (Hirano et al. 2024). Cryo-EM structures of human SID-1 reveal implications for their low-pH-dependent RNA transport activity (Zheng et al. 2024). New structure-dynamic clues underlie the regulatory diversity among tissue-specific NCX variants (Giladi et al. 2024). N-glycosylation plays a functional role in SIDT1-mediated RNA uptake (Yang et al. 2024).