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TitleStructure of the human systemic RNAi defective transmembrane protein 1 (hSIDT1) reveals the conformational flexibility of its lipid binding domain.
Journal, issue, pagesbioRxiv, Year 2024
Publish dateJun 12, 2024
AuthorsVikas Navratna / Arvind Kumar / Jaimin K Rana / Shyamal Mosalaganti /
PubMed AbstractIn , inter-cellular transport of the small non-coding RNA causing systemic RNA interference (RNAi) is mediated by the transmembrane protein SID1, encoded by the gene in the systemic RNA interference- ...In , inter-cellular transport of the small non-coding RNA causing systemic RNA interference (RNAi) is mediated by the transmembrane protein SID1, encoded by the gene in the systemic RNA interference-defective () loci. SID1 shares structural and sequence similarity with cholesterol uptake protein 1 (CHUP1) and is classified as a member of the cholesterol uptake family (ChUP). Although systemic RNAi is not an evolutionarily conserved process, the gene products are found across the animal kingdom, suggesting the existence of other novel gene regulatory mechanisms mediated by small non-coding RNAs. Human homologs of gene products - hSIDT1 and hSIDT2 - mediate contact-dependent lipophilic small non-coding dsRNA transport. Here, we report the structure of recombinant human SIDT1. We find that the extra-cytosolic domain (ECD) of hSIDT1 adopts a double jelly roll fold, and the transmembrane domain (TMD) exists as two modules - a flexible lipid binding domain (LBD) and a rigid TMD core. Our structural analyses provide insights into the inherent conformational dynamics within the lipid binding domain in cholesterol uptake (ChUP) family members.
External linksbioRxiv / PubMed:38187772 / PubMed Central
MethodsEM (single particle)
Resolution3.5 Å
Structure data

42943

8v38

EMDB-42943, PDB-8v38:
Structure of the human systemic RNAi defective transmembrane protein 1 (hSIDT1)
Method: EM (single particle) / Resolution: 3.5 Å

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / RNA interference / transmembrane protein / cholesterol or dsRNA uptake family.

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