5E3H

Structural Basis for RNA Recognition and Activation of RIG-I

「3TMI」から置き換えられました

5E3H の概要

• エントリーDOI: 10.2210/pdb5e3h/pdb
• 関連するPDBエントリー: 3TMI
• 分子名称: 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)
• 機能のキーワード: 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
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 89273.81

構造登録者

Jiang, F.,Miller, M.T.,Marcotrigiano, J. (登録日: 2015-10-02, 公開日: 2015-11-18, 最終更新日: 2023-09-27)

主引用文献

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

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: 21947008
DOI: 10.1038/nature10537

実験手法

X-RAY DIFFRACTION (2.7 Å)