8Z0P

Cryo-EM structure of human ELAC2

Summary for 8Z0P

• Entry DOI: 10.2210/pdb8z0p/pdb
• EMDB information: 39710
• Descriptor: Zinc phosphodiesterase ELAC protein 2, ZINC ION, PHOSPHATE ION (3 entities in total)
• Functional Keywords: endonuclease zinc phosphodiesterase, rna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 92573.91

Authors

Liu, Z.M.,Xue, C.Y. (deposition date: 2024-04-10, release date: 2024-12-18, Last modification date: 2025-06-25)

Primary citation

Xue, C.,Tian, J.,Chen, Y.,Liu, Z.
Structural insights into human ELAC2 as a tRNA 3' processing enzyme.
Nucleic Acids Res., 52:13434-13446, 2024

PubMed Abstract: Human elaC ribonuclease Z 2 (ELAC2) removes the 3' trailer of precursor transfer ribonucleic acid (pre-tRNA). Mutations in ELAC2 are highly associated with the development of prostate cancer and hypertrophic cardiomyopathy. However, the catalytic mechanism of ELAC2 remains unclear. We determined the cryogenic electron microscopy structures of human ELAC2 in various states, including the apo, pre-tRNA-bound and tRNA-bound states, which enabled us to identify the structural basis for its binding to pre-tRNA and cleavage of the 3' trailer. Notably, conformational rearrangement of the C-terminal helix was related to feeding of the 3' trailer into the cleavage site, possibly explaining why its mutations are associated with disease. We further used biochemical assays to analyse the structural effects of disease-related mutations of human ELAC2. Collectively, our data provide a comprehensive structural basis for how ELAC2 recruits pre-tRNA via its flexible arm domain and guides the 3' trailer of pre-tRNA into the active centre for cleavage by its C-terminal helix.

PubMed: 39494506
DOI: 10.1093/nar/gkae1014

Experimental method

ELECTRON MICROSCOPY (3.1 Å)