Summary for 5E3H
| Entry DOI | 10.2210/pdb5e3h/pdb |
| Related | 3TMI |
| Descriptor | Probable ATP-dependent RNA helicase DDX58, RNA (5'-R(*CP*GP*AP*CP*GP*CP*UP*AP*GP*CP*GP*U)-3'), ZINC ION, ... (7 entities in total) |
| Functional Keywords | adenosine triphosphatases, adenosine triphosphate, dead-box rna helicases, enzyme activation, fluorometry, humans, immunity, innate, models, molecular, nucleic acid conformation, pliability, protein binding, protein structure, tertiary, proteolysis, rna, double-stranded, rna-binding proteins, scattering, small angle, structure-activity relationship, substrate specificity, trypsin, hydrolase, hydrolase-rna complex, hydrolase/rna |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 89273.81 |
| Authors | Jiang, F.,Miller, M.T.,Marcotrigiano, J. (deposition date: 2015-10-02, release date: 2015-11-18, Last modification date: 2023-09-27) |
| Primary citation | Jiang, F.,Ramanathan, A.,Miller, M.T.,Tang, G.Q.,Gale, M.,Patel, S.S.,Marcotrigiano, J. Structural basis of RNA recognition and activation by innate immune receptor RIG-I. Nature, 479:423-427, 2011 Cited by PubMed Abstract: Retinoic-acid-inducible gene-I (RIG-I; also known as DDX58) is a cytoplasmic pathogen recognition receptor that recognizes pathogen-associated molecular pattern (PAMP) motifs to differentiate between viral and cellular RNAs. RIG-I is activated by blunt-ended double-stranded (ds)RNA with or without a 5'-triphosphate (ppp), by single-stranded RNA marked by a 5'-ppp and by polyuridine sequences. Upon binding to such PAMP motifs, RIG-I initiates a signalling cascade that induces innate immune defences and inflammatory cytokines to establish an antiviral state. The RIG-I pathway is highly regulated and aberrant signalling leads to apoptosis, altered cell differentiation, inflammation, autoimmune diseases and cancer. The helicase and repressor domains (RD) of RIG-I recognize dsRNA and 5'-ppp RNA to activate the two amino-terminal caspase recruitment domains (CARDs) for signalling. Here, to understand the synergy between the helicase and the RD for RNA binding, and the contribution of ATP hydrolysis to RIG-I activation, we determined the structure of human RIG-I helicase-RD in complex with dsRNA and an ATP analogue. The helicase-RD organizes into a ring around dsRNA, capping one end, while contacting both strands using previously uncharacterized motifs to recognize dsRNA. Small-angle X-ray scattering, limited proteolysis and differential scanning fluorimetry indicate that RIG-I is in an extended and flexible conformation that compacts upon binding RNA. These results provide a detailed view of the role of helicase in dsRNA recognition, the synergy between the RD and the helicase for RNA binding and the organization of full-length RIG-I bound to dsRNA, and provide evidence of a conformational change upon RNA binding. The RIG-I helicase-RD structure is consistent with dsRNA translocation without unwinding and cooperative binding to RNA. The structure yields unprecedented insight into innate immunity and has a broader impact on other areas of biology, including RNA interference and DNA repair, which utilize homologous helicase domains within DICER and FANCM. PubMed: 21947008DOI: 10.1038/nature10537 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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