1r36
From Proteopedia
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| - | [[Image:1r36.gif|left|200px]] | + | [[Image:1r36.gif|left|200px]] |
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| - | '''NMR-based structure of autoinhibited murine Ets-1 deltaN301''' | + | {{Structure |
| + | |PDB= 1r36 |SIZE=350|CAPTION= <scene name='initialview01'>1r36</scene> | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
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| + | '''NMR-based structure of autoinhibited murine Ets-1 deltaN301''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1R36 is a [ | + | 1R36 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entries 1ETC and 1ETD. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R36 OCA]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15591056 15591056] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: transcription factor; autoinhibition module; winged helix-turn-helix; helical bundle]] | [[Category: transcription factor; autoinhibition module; winged helix-turn-helix; helical bundle]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:46:13 2008'' |
Revision as of 11:46, 20 March 2008
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NMR-based structure of autoinhibited murine Ets-1 deltaN301
Overview
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.
About this Structure
1R36 is a Single protein structure of sequence from Mus musculus. This structure supersedes the now removed PDB entries 1ETC and 1ETD. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Mar 20 13:46:13 2008
