8HIP

dsRNA transporter

Summary for 8HIP

• Entry DOI: 10.2210/pdb8hip/pdb
• EMDB information: 34825
• Descriptor: Systemic RNA interference defective protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate, ... (4 entities in total)
• Functional Keywords: dsrna transporter, rna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 180755.55

Authors

Jiang, D.H.,Zhang, J.T. (deposition date: 2022-11-21, release date: 2023-11-29, Last modification date: 2025-06-25)

Primary citation

Zhang, J.,Zhan, C.,Fan, J.,Wu, D.,Zhang, R.,Wu, D.,Chen, X.,Lu, Y.,Li, M.,Lin, M.,Gong, J.,Jiang, D.
Structural insights into double-stranded RNA recognition and transport by SID-1.
Nat.Struct.Mol.Biol., 31:1095-1104, 2024

PubMed Abstract: RNA uptake by cells is critical for RNA-mediated gene interference (RNAi) and RNA-based therapeutics. In Caenorhabditis elegans, RNAi is systemic as a result of SID-1-mediated double-stranded RNA (dsRNA) across cells. Despite the functional importance, the underlying mechanisms of dsRNA internalization by SID-1 remain elusive. Here we describe cryogenic electron microscopy structures of SID-1, SID-1-dsRNA complex and human SID-1 homologs SIDT1 and SIDT2, elucidating the structural basis of dsRNA recognition and import by SID-1. The homodimeric SID-1 homologs share conserved architecture, but only SID-1 possesses the molecular determinants within its extracellular domains for distinguishing dsRNA from single-stranded RNA and DNA. We show that the removal of the long intracellular loop between transmembrane helix 1 and 2 attenuates dsRNA uptake and systemic RNAi in vivo, suggesting a possible endocytic mechanism of SID-1-mediated dsRNA internalization. Our study provides mechanistic insights into dsRNA internalization by SID-1, which may facilitate the development of dsRNA applications based on SID-1.

PubMed: 38664565
DOI: 10.1038/s41594-024-01276-9

Experimental method

ELECTRON MICROSCOPY (2.77 Å)