8a11 | pdb_00008a11

Cryo-EM structure of the Human SHMT1-RNA complex

spinqualitylabelsall models 8a11, resolution 3.52Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8a11 is a 4 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 3.52Å Ligands: PLP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLYC_HUMAN Interconversion of serine and glycine. Publication Abstract from PubMed RNA can directly control protein activity in a process called riboregulation; only a few mechanisms of riboregulation have been described in detail, none of which have been characterized on structural grounds. Here, we present a comprehensive structural, functional, and phylogenetic analysis of riboregulation of cytosolic serine hydroxymethyltransferase (SHMT1), the enzyme interconverting serine and glycine in one-carbon metabolism. We have determined the cryoelectron microscopy (cryo-EM) structure of human SHMT1 in its free- and RNA-bound states, and we show that the RNA modulator competes with polyglutamylated folates and acts as an allosteric switch, selectively altering the enzyme's reactivity vs. serine. In addition, we identify the tetrameric assembly and a flap structural motif as key structural elements necessary for binding of RNA to eukaryotic SHMT1. The results presented here suggest that riboregulation may have played a role in evolution of eukaryotic SHMT1 and in compartmentalization of one-carbon metabolism. Our findings provide insights for RNA-based therapeutic strategies targeting this cancer-linked metabolic pathway. Structure-based mechanism of riboregulation of the metabolic enzyme SHMT1.,Spizzichino S, Di Fonzo F, Marabelli C, Tramonti A, Chaves-Sanjuan A, Parroni A, Boumis G, Liberati FR, Paone A, Montemiglio LC, Ardini M, Jakobi AJ, Bharadwaj A, Swuec P, Tartaglia GG, Paiardini A, Contestabile R, Mai A, Rotili D, Fiorentino F, Macone A, Giorgi A, Tria G, Rinaldo S, Bolognesi M, Giardina G, Cutruzzola F Mol Cell. 2024 Jul 9:S1097-2765(24)00523-9. doi: 10.1016/j.molcel.2024.06.016. PMID:38996576 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serine hydroxymethyltransferase 3D structures

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