7y63 | pdb_00007y63
ApoSIDT2-pH7.4
Structural highlights
FunctionSIDT2_HUMAN Mediates the translocation of RNA and DNA across the lysosomal membrane during RNA and DNA autophagy (RDA), a process in which RNA or DNA is directly imported into lysosomes in an ATP-dependent manner, and degraded (PubMed:27046251, PubMed:27846365). Involved in the uptake of single-stranded oligonucleotides by living cells, a process called gymnosis (PubMed:28277980). In vitro, mediates the uptake of linear DNA more efficiently than that of circular DNA, but exhibits similar uptake efficacy toward RNA and DNA. Binds long double-stranded RNA (dsRNA) (500 - 700 base pairs), but not dsRNA shorter than 100 bp (By similarity).[UniProtKB:Q8CIF6][1] [2] [3] Publication Abstract from PubMedThe systemic RNAi-defective (SID) transmembrane family member 2 (SIDT2) is a putative nucleic acid channel or transporter that plays essential roles in nucleic acid transport and lipid metabolism. Here, we report the cryo-electron microscopy (EM) structures of human SIDT2, which forms a tightly packed dimer with extensive interactions mediated by two previously uncharacterized extracellular/luminal beta-strand-rich domains and the unique transmembrane domain (TMD). The TMD of each SIDT2 protomer contains eleven transmembrane helices (TMs), and no discernible nucleic acid conduction pathway has been identified within the TMD, suggesting that it may act as a transporter. Intriguingly, TM3-6 and TM9-11 form a large cavity with a putative catalytic zinc atom coordinated by three conserved histidine residues and one aspartate residue lying approximately 6 A from the extracellular/luminal surface of the membrane. Notably, SIDT2 can hydrolyze C18 ceramide into sphingosine and fatty acid with a slow rate. The information presented advances the understanding of the structure-function relationships in the SID1 family proteins. Structural insight into the human SID1 transmembrane family member 2 reveals its lipid hydrolytic activity.,Qian D, Cong Y, Wang R, Chen Q, Yan C, Gong D Nat Commun. 2023 Jun 15;14(1):3568. doi: 10.1038/s41467-023-39335-2. PMID:37322007[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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