1r36

NMR-based structure of autoinhibited murine Ets-1 deltaN301

spinqualitylabelsall models 1r36 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1r36 is a 1 chain structure with sequence from Mus musculus. This structure supersedes the now removed PDB entries 1etc and 1etd. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ETS1_MOUSE Transcription factor. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The transcription factor Ets-1 is regulated by the allosteric coupling of DNA binding with the unfolding of an alpha-helix (HI-1) within an autoinhibitory module. To understand the structural and dynamic basis for this autoinhibition, we have used NMR spectroscopy to characterize Ets-1DeltaN301, a partially inhibited fragment of Ets-1. The NMR-derived Ets-1DeltaN301 structure reveals that the autoinhibitory module is formed predominantly by the hydrophobic packing of helices from the N-terminal (HI-1, HI-2) and C-terminal (H4, H5) inhibitory sequences, along with H1 of the intervening DNA binding ETS domain. The intramolecular interactions made by HI-1 in Ets-1DeltaN301 are similar to the intermolecular contacts observed in the crystal structure of an Ets-1DeltaN300 dimer, confirming that the latter represents a domain-swapped species. (15)N relaxation studies demonstrate that the backbone of the N-terminal inhibitory sequence is mobile on the nanosecond-picosecond and millisecond-microsecond time scales. Furthermore, hydrogen exchange measurements reveal that amide protons in helices HI-1 and HI-2 exchange with water at rates only approximately 15- and approximately 75-fold slower, respectively, than predicted for an unfolded polypeptide. These findings indicate that inhibitory helices are only marginally stable even in the absence of DNA. The energetic coupling of DNA binding with the facile unfolding of the labile HI-1 provides a mechanism for modulating Ets-1 DNA binding activity via protein partnerships, post-translational modifications, or mutations. Ets-1 autoinhibition illustrates how conformational equilibria within structural domains can regulate macromolecular interactions. The structural and dynamic basis of Ets-1 DNA binding autoinhibition.,Lee GM, Donaldson LW, Pufall MA, Kang HS, Pot I, Graves BJ, McIntosh LP J Biol Chem. 2005 Feb 25;280(8):7088-99. Epub 2004 Dec 9. PMID:15591056 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ets1

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