9FTW
Crystal structure of calcium-activated EndoU
Summary for 9FTW
| Entry DOI | 10.2210/pdb9ftw/pdb |
| Descriptor | Uridylate-specific endoribonuclease, ACETATE ION, CALCIUM ION, ... (5 entities in total) |
| Functional Keywords | calcium, rna binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 94378.31 |
| Authors | |
| Primary citation | 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 Cited by 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: 39070628DOI: 10.21203/rs.3.rs-4654759/v1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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