7LT1

Structure of the cGAS-like receptor human MB21D2

7LT1 の概要

• エントリーDOI: 10.2210/pdb7lt1/pdb
• 分子名称: Protein MB21D2, SULFATE ION (2 entities in total)
• 機能のキーワード: cgas-like receptor, cglr, nucleotidyltransferase, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 107468.78

構造登録者

Morehouse, B.R.,Slavik, K.M.,Kranzusch, P.J. (登録日: 2021-02-18, 公開日: 2021-07-21, 最終更新日: 2024-10-23)

主引用文献

Slavik, K.M.,Morehouse, B.R.,Ragucci, A.E.,Zhou, W.,Ai, X.,Chen, Y.,Li, L.,Wei, Z.,Bahre, H.,Konig, M.,Seifert, R.,Lee, A.S.Y.,Cai, H.,Imler, J.L.,Kranzusch, P.J.
cGAS-like receptors sense RNA and control 3'2'-cGAMP signalling in Drosophila.
Nature, 597:109-113, 2021

PubMed Abstract: Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2'-5']pA[3'-5']p (2'3'-cGAMP) and controls activation of innate immunity in mammalian cells. Animal genomes typically encode multiple proteins with predicted homology to cGAS, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'-5']pA[2'-5']p (3'2'-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3'2'-cGAMP explains selective isomer recognition, and 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.

PubMed: 34261127
DOI: 10.1038/s41586-021-03743-5

実験手法

X-RAY DIFFRACTION (2.4 Å)