EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Molecular basis of autoimmune disease protection by MDA5 variants.
ジャーナル・号・ページ	Cell Rep, Vol. 44, Issue 6, Page 115754, Year 2025
掲載日	2025年5月30日
著者	Rahul Singh / Joe D Joiner / Alba Herrero Del Valle / Marleen Zwaagstra / Ida Jobe / Brian J Ferguson / Frank J M van Kuppeveld / Yorgo Modis /
PubMed 要旨	MDA5 recognizes double-stranded RNA (dsRNA) from viruses and retroelements. Cooperative filament formation and ATP-dependent proofreading confer MDA5 with the necessary sensitivity and specificity ...MDA5 recognizes double-stranded RNA (dsRNA) from viruses and retroelements. Cooperative filament formation and ATP-dependent proofreading confer MDA5 with the necessary sensitivity and specificity for dsRNA. Many MDA5 genetic variants are associated with protection from autoimmune disease while increasing the risk of infection and chronic inflammation. How these variants affect RNA sensing remains unclear. Here, we determine the consequences of autoimmune-protective variants on the molecular structure and activities of MDA5. Rare variants E627 and I923V reduce the interferon response to picornavirus infection. E627 does not bind RNA. I923V is ATPase hyperactive, causing premature dissociation from dsRNA. Cryoelectron microscopy (cryo-EM) structures of MDA5 I923V bound to dsRNA at different stages of ATP hydrolysis reveal smaller RNA binding interfaces, leading to excessive proofreading activity. Variants R843H and T946A, which are genetically linked and cause mild phenotypes, did not affect cytokine induction, suggesting an indirect disease mechanism. In conclusion, autoimmune-protective MDA5 variants dampen MDA5-dependent signaling via multiple mechanisms.
リンク	Cell Rep / PubMed:40450684 / PubMed Central
手法	EM (らせん対称)
解像度	3.35 - 4.21 Å
構造データ	50111 9f0j EMDB-50111, PDB-9f0j: Cryo-EM structure of the I923V MDA5-dsRNA filament without nucleotide 手法: EM (らせん対称) / 解像度: 3.35 Å 50136 9f1u EMDB-50136, PDB-9f1u: Cryo-EM structure of the I923V MDA5-dsRNA filament with ADP-AlF4 bound and 81-degree helical twist 手法: EM (らせん対称) / 解像度: 3.67 Å 50137 9f20 EMDB-50137, PDB-9f20: Cryo-EM structure of the I923V MDA5-dsRNA filament with ADP-AlF4 bound and 88-degree helical twist 手法: EM (らせん対称) / 解像度: 4.13 Å 50150 9f2l EMDB-50150, PDB-9f2l: Cryo-EM structure of the I923V MDA5-dsRNA filament with ADP-AlF4 bound and 73-degree helical twist 手法: EM (らせん対称) / 解像度: 3.86 Å 50165 9f2w EMDB-50165, PDB-9f2w: Cryo-EM structure of the I923V MDA5-dsRNA filament in complex with ATP 手法: EM (らせん対称) / 解像度: 4.21 Å 50175 9f3p EMDB-50175, PDB-9f3p: Cryo-EM structure of the A946T MDA5-dsRNA filament 手法: EM (らせん対称) / 解像度: 3.97 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子YM ChemComp-ALF: TETRAFLUOROALUMINATE ION / テトラフルオロアルミナ-ト ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM
由来	mus musculus (ハツカネズミ)
キーワード	IMMUNE SYSTEM / PROTEIN-RNA COMPLEX / HELICAL FILAMENT / ATPASE / INNATE IMMUNE RECEPTOR