21zh

Cryo-EM structure of NSUN2-tRNAlys-SAM

spinqualitylabelsall models 21zh, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 21zh is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.9Å Ligands: SAM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The human RNA m(5)C methyltransferase NSUN2 catalyzes site-specific cytosine methylation across diverse RNA substrates and thereby regulates a wide range of biological and physiological processes. However, the molecular basis by which NSUN2 achieves broad substrate recognition while maintaining catalytic specificity has remained unclear. Here, we determine structures of human NSUN2 in both substrate-free and substrate-bound states using X-ray crystallography and cryo-electron microscopy. Structures of NSUN2 in complex with multiple tRNA substrates reveal a structure-first, sequence-tolerant strategy in which NSUN2 actively remodels tRNA architecture, exposing the buried target cytosine and positioning it within the catalytic pocket for methyl transfer. This recognition strategy enables NSUN2 to accommodate diverse tRNA substrates through a largely conserved interaction interface. Together, our findings define the molecular principles underlying NSUN2-mediated RNA m(5)C modification. Structure-driven RNA remodeling underlies broad substrate recognition by NSUN2.,Hu Q, Yang W, Yu Y, Yi R, Zhang Y, Duan L, Li F, Zhang K, Gong Q, Li S Sci China Life Sci. 2026 May 26. doi: 10.1007/s11427-026-3373-3. PMID:42258135 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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