Molecular basis for the calcium-dependent activation of the ribonuclease EndoU

Molecular basis for the calcium-dependent activation of the ribonuclease EndoU

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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, aftermath cabernet sauvignon 2017 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 use biophysical and computational techniques along with in vitro assays to investigate the calcium-dependent activation of human EndoU.We determine the crystal structure of EndoU bound to calcium and find 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 6love luzern across all eukaryotic EndoUs, highlighting a unique evolutionary adaptation that connects endoribonuclease activity to cellular signaling in eukaryotes.