7UCW

Structure of mouse Decr1 in complex with 2'-5' oligoadenylate

7UCW の概要

• エントリーDOI: 10.2210/pdb7ucw/pdb
• 分子名称: Decr1 protein, [[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl]oxy-3-hydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl]oxy-3-hydroxy-oxolan-2-yl]methoxy-hydroxy-phosphoryl] phosphono hydrogen phosphate (3 entities in total)
• 機能のキーワード: immunity, oxidoreductase
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 134619.71

構造登録者

Govande, A.A.,Kranzusch, P.J. (登録日: 2022-03-17, 公開日: 2023-03-22, 最終更新日: 2023-10-25)

主引用文献

Govande, A.A.,Babnis, A.W.,Urban, C.,Habjan, M.,Hartmann, R.,Kranzusch, P.J.,Pichlmair, A.
RNase L-activating 2'-5' oligoadenylates bind ABCF1, ABCF3 and Decr-1.
J.Gen.Virol., 104:-, 2023

PubMed Abstract: A notable signalling mechanism employed by mammalian innate immune signalling pathways uses nucleotide-based second messengers such as 2'3'-cGAMP and 2'-5'-oligoadenylates (OAs), which bind and activate STING and RNase L, respectively. Interestingly, the involvement of nucleotide second messengers to activate antiviral responses is evolutionarily conserved, as evidenced by the identification of an antiviral cGAMP-dependent pathway in . Using a mass spectrometry approach, we identified several members of the ABCF family in human, mouse and cell lysates as 2'-5' OA-binding proteins, suggesting an evolutionarily conserved function. Biochemical characterization of these interactions demonstrates high-affinity binding of 2'-5' OA to ABCF1, dependent on phosphorylated 2'-5' OA and an intact Walker A/B motif of the ABC cassette of ABCF1. As further support for species-specific interactions with 2'-5' OA, we additionally identified that the metabolic enzyme Decr1 from mouse, but not human or cells, forms a high-affinity complex with 2'-5' OA. A 1.4 Å co-crystal structure of the mouse Decr1-2'-5' OA complex explains high-affinity recognition of 2'-5' OA and the mechanism of species specificity. Despite clear evidence of physical interactions, we could not identify profound antiviral functions of ABCF1, ABCF3 or Decr1 or 2'-5' OA-dependent regulation of cellular translation rates, as suggested by the engagement of ABCF proteins. Thus, although the biological consequences of the here identified interactions need to be further studied, our data suggest that 2'-5' OA can serve as a signalling hub to distribute a signal to different recipient proteins.

PubMed: 37676257
DOI: 10.1099/jgv.0.001890

実験手法

X-RAY DIFFRACTION (1.35 Å)