8gxc

Crystal structure of NAD+ -II riboswitch in complex with NMN

spinqualitylabelsall models 8gxc, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8gxc is a 7 chain structure with sequence from Homo sapiens and Streptococcus sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GTP, MG, NMN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SNRPA_HUMAN Binds stem loop II of U1 snRNA. It is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. Binds preferentially to the 5'-UGCAC-3' motif in vitro. Publication Abstract from PubMed Riboswitches are conserved non-coding domains in bacterial mRNA with gene regulation function that are essential for maintaining enzyme co-factor metabolism. Recently, the pnuC RNA motif was reported to selectively bind nicotinamide adenine dinucleotide (NAD+), defining a novel class of NAD+ riboswitches (NAD+-II) according to phylogenetic analysis. To reveal the three-dimensional architecture and the ligand-binding mode of this riboswitch, we solved the crystal structure of NAD+-II riboswitch in complex with NAD+. Strikingly and in contrast to class-I riboswitches that form a tight recognition pocket for the adenosine diphosphate (ADP) moiety of NAD+, the class-II riboswitches form a binding pocket for the nicotinamide mononucleotide (NMN) portion of NAD+ and display only unspecific interactions with the adenosine. We support this finding by an additional structure of the class-II RNA in complex with NMN alone. The structures define a novel RNA tertiary fold that was further confirmed by mutational analysis in combination with isothermal titration calorimetry (ITC), and 2-aminopurine-based fluorescence spectroscopic folding studies. Furthermore, we truncated the pnuC RNA motif to a short RNA helical scaffold with binding affinity comparable to the wild-type motif to allude to the potential of engineering the NAD+-II motif for biotechnological applications. Structure-based investigations of the NAD+-II riboswitch.,Xu X, Egger M, Li C, Chen H, Micura R, Ren A Nucleic Acids Res. 2023 Jan 11;51(1):54-67. doi: 10.1093/nar/gkac1227. PMID:36610789 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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