9FTW

Crystal structure of calcium-activated EndoU

9FTW の概要

• エントリーDOI: 10.2210/pdb9ftw/pdb
• 分子名称: Uridylate-specific endoribonuclease, ACETATE ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: calcium, rna binding protein
• 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: 94378.31

構造登録者

Fribourg, S.,Campagne, S. (登録日: 2024-06-25, 公開日: 2024-08-14)

主引用文献

Malard, F.,Dias, K.,Baudy, M.,Thore, S.,Vialet, B.,Barthelemy, P.,Fribourg, S.,Karginov, F.V.,Campagne, S.
Molecular Basis for the Calcium-Dependent Activation of the Ribonuclease EndoU.
Res Sq, 2024

PubMed Abstract: Ribonucleases (RNases) are ubiquitous enzymes that process or degrade RNA, essential for cellular functions and immune responses. The EndoU-like superfamily includes endoribonucleases conserved across bacteria, eukaryotes, and certain viruses, with an ancient evolutionary link to the ribonuclease A-like superfamily. Both bacterial EndoU and animal RNase A share a similar fold and function independently of cofactors. In contrast, the eukaryotic EndoU catalytic domain requires divalent metal ions for catalysis, possibly due to an N-terminal extension near the catalytic core. In this study, we used biophysical and computational techniques along with assays to investigate the calcium-dependent activation of human EndoU. We determined the crystal structure of EndoU bound to calcium and found that calcium binding remote from the catalytic triad triggers water-mediated intramolecular signaling and structural changes, activating the enzyme through allostery. Calcium-binding involves residues from both the catalytic core and the N-terminal extension, indicating that the N-terminal extension interacts with the catalytic core to modulate activity in response to calcium. Our findings suggest that similar mechanisms may be present across all eukaryotic EndoUs, highlighting a unique evolutionary adaptation that connects endoribonuclease activity to cellular signaling in eukaryotes.

PubMed: 39070628
DOI: 10.21203/rs.3.rs-4654759/v1

実験手法

X-RAY DIFFRACTION (1.65 Å)