4e58

Crystal structure of GCC(LCG)CCGC duplex containing LNA residue

spinqualitylabelsall models 4e58, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4e58 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: LCG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed CCG repeats are highly over-represented in exons of the human genome. Usually they are located in the 5' UTR but are also abundant in translated sequences. The CCG repeats are associated with three tri-nucleotide repeat disorders: Huntington's disease, myotonic dystrophy type 1 and chromosome X-linked mental retardation (FRAXE). In this study, we present two crystal structures containing double-stranded CCG repeats: one of an RNA in the native form, and one containing LNA nucleotides. Both duplexes form A-helices but with strands slipped in the 5' (native structure) or the 3' direction (LNA-containing structure). As a result, one of two expected C-C pairs is eliminated from the duplex. Each of the three observed C-C pairs interacts differently, forming either one weak H-bond or none. LNA nucleotides have no apparent effect on the helical parameters but the base stacking is increased compared to the native duplex and the distribution of electrostatic potential in the major groove is changed. The CCG crystal structures explain the thermodynamic fragility of CCG runs and throw light on the observation that the MBNL1 protein recognises CCG runs, as well as CUG and CAG, but not the relatively stable CGG repeats. Crystallographic characterization of CCG repeats.,Kiliszek A, Kierzek R, Krzyzosiak WJ, Rypniewski W Nucleic Acids Res. 2012 Sep;40(16):8155-62. doi: 10.1093/nar/gks557. Epub 2012, Jun 19. PMID:22718980 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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