9B89
Cryo-EM structure of human ADAR1 in complex with dsRNA derived from HT2C gene in the pre-editing state
Summary for 9B89
| Entry DOI | 10.2210/pdb9b89/pdb |
| EMDB information | 44335 |
| Descriptor | Maltodextrin-binding protein,Double-stranded RNA-specific adenosine deaminase, RNA (71-MER), INOSITOL HEXAKISPHOSPHATE, ... (4 entities in total) |
| Functional Keywords | adar1-dsrna complex, pre-editing state, hydrolase-rna complex, hydrolase/rna |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 3 |
| Total formula weight | 354766.53 |
| Authors | |
| Primary citation | Deng, X.,Sun, L.,Zhang, M.,Basavaraj, R.,Wang, J.,Weng, Y.L.,Gao, Y. Biochemical profiling and structural basis of ADAR1-mediated RNA editing. Mol.Cell, 85:1381-1394.e6, 2025 Cited by PubMed Abstract: ADAR1 regulates RNA-induced immune responses by converting adenosine to inosine in double-stranded RNA. Mutations in ADAR1 are associated with human autoimmune disease, and targeting ADAR1 has been proposed for cancer immunotherapy. However, the molecular mechanisms underlying ADAR1-mediated editing remain unclear. Here, we provide detailed biochemical and structural characterizations of human ADAR1. Our biochemical profiling reveals that ADAR1 editing is both sequence and RNA-duplex-length dependent but can well tolerate mismatches near the editing site. High-resolution ADAR1-RNA complex structures, combined with mutagenesis, elucidate RNA binding, substrate selection, dimerization, and the essential role of RNA-binding domain 3. The ADAR1 structures also help explain the potential defects of disease-associated mutations, where biochemical and RNA sequencing analysis further indicate some of the mutations preferentially impact the editing of RNAs with short duplexes. These findings unveil the molecular basis of ADAR1 editing and provide insights into its immune-regulatory functions and therapeutic potential. PubMed: 40101712DOI: 10.1016/j.molcel.2025.02.017 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.87 Å) |
Structure validation
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