8S24

Structure of the E3 ubiquitin ligase RNF213, determined by cryoEM

8S24 の概要

• エントリーDOI: 10.2210/pdb8s24/pdb
• EMDBエントリー: 19653
• 分子名称: E3 ubiquitin-protein ligase RNF213, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: e3 ubiquitin ligase, atpase, carbohydrate-binding domain, ring domain, rz domain, antimicrobial protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 597048.15

構造登録者

Naydenova, K.,Randow, F. (登録日: 2024-02-16, 公開日: 2024-10-09, 最終更新日: 2025-07-09)

主引用文献

Crespillo-Casado, A.,Pothukuchi, P.,Naydenova, K.,Yip, M.C.J.,Young, J.M.,Boulanger, J.,Dharamdasani, V.,Harper, C.,Hammoudi, P.M.,Otten, E.G.,Boyle, K.,Gogoi, M.,Malik, H.S.,Randow, F.
Recognition of phylogenetically diverse pathogens through enzymatically amplified recruitment of RNF213.
Embo Rep., 25:4979-5005, 2024

PubMed Abstract: Innate immunity senses microbial ligands known as pathogen-associated molecular patterns (PAMPs). Except for nucleic acids, PAMPs are exceedingly taxa-specific, thus enabling pattern recognition receptors to detect cognate pathogens while ignoring others. How the E3 ubiquitin ligase RNF213 can respond to phylogenetically distant pathogens, including Gram-negative Salmonella, Gram-positive Listeria, and eukaryotic Toxoplasma, remains unknown. Here we report that the evolutionary history of RNF213 is indicative of repeated adaptation to diverse pathogen target structures, especially in and around its newly identified CBM20 carbohydrate-binding domain, which we have resolved by cryo-EM. We find that RNF213 forms coats on phylogenetically distant pathogens. ATP hydrolysis by RNF213's dynein-like domain is essential for coat formation on all three pathogens studied as is RZ finger-mediated E3 ligase activity for bacteria. Coat formation is not diffusion-limited but instead relies on rate-limiting initiation events and subsequent cooperative incorporation of further RNF213 molecules. We conclude that RNF213 responds to evolutionarily distant pathogens through enzymatically amplified cooperative recruitment.

PubMed: 39375464
DOI: 10.1038/s44319-024-00280-w

実験手法

ELECTRON MICROSCOPY (3 Å)