6gd3 | pdb_00006gd3

Structure of HuR RRM3 in complex with RNA (UAUUUA)

spinqualitylabelsall models 6gd3, resolution 1.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6gd3 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NA Gene: ELAVL1, HUR (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ELAV1_HUMAN] Involved in 3'-UTR ARE-mediated MYC stabilization. Binds avidly to the AU-rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, HUR binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA and AUUUUUA motifs. Binds preferentially to the 5'-UUUU[AG]UUU-3' motif in vitro. Publication Abstract from PubMed HuR/ELAVL1 is an RNA-binding protein involved in differentiation and stress response that acts primarily by stabilizing messenger RNA (mRNA) targets. HuR comprises three RNA recognition motifs (RRMs) where the structure and RNA binding of RRM3 and of full-length HuR remain poorly understood. Here, we report crystal structures of RRM3 free and bound to cognate RNAs. Our structural, NMR and biochemical data show that RRM3 mediates canonical RNA interactions and reveal molecular details of a dimerization interface localized on the alpha-helical face of RRM3. NMR and SAXS analyses indicate that the three RRMs in full-length HuR are flexibly connected in the absence of RNA, while they adopt a more compact arrangement when bound to RNA. Based on these data and crystal structures of tandem RRM1,2-RNA and our RRM3-RNA complexes, we present a structural model of RNA recognition involving all three RRM domains of full-length HuR. Mutational analysis demonstrates that RRM3 dimerization and RNA binding is required for functional activity of full-length HuR in vitro and to regulate target mRNAs levels in human cells, thus providing a fine-tuning for HuR activity in vivo. HuR biological function involves RRM3-mediated dimerization and RNA binding by all three RRMs.,Pabis M, Popowicz GM, Stehle R, Fernandez-Ramos D, Asami S, Warner L, Garcia-Maurino SM, Schlundt A, Martinez-Chantar ML, Diaz-Moreno I, Sattler M Nucleic Acids Res. 2019 Jan 25;47(2):1011-1029. doi: 10.1093/nar/gky1138. PMID:30418581 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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