Novel DNA-binding element within the C-terminal extension of the nuclear receptor DNA-binding domain |
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Authors: | Jakób Michał Kołodziejczyk Robert Orłowski Marek Krzywda Szymon Kowalska Agnieszka Dutko-Gwóźdź Joanna Gwóźdź Tomasz Kochman Marian Jaskólski Mariusz Ozyhar Andrzej |
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Institution: | Michał Jakób, Robert Kołodziejczyk, Marek Orłowski, Szymon Krzywda, Agnieszka Kowalska, Joanna Dutko-Gwóźdź, Tomasz Gwóźdź, Marian Kochman, Mariusz Jaskólski, and Andrzej Ożyhar |
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Abstract: | The heterodimer of the ecdysone receptor (EcR) and ultraspiracle (Usp), members of the nuclear receptors superfamily, is considered as the functional receptor for ecdysteroids initiating molting and metamorphosis in insects. Here we report the 1.95 Å structure of the complex formed by the DNA-binding domains (DBDs) the EcR and the Usp, bound to the natural pseudopalindromic response element. Comparison of the structure with that obtained previously, using an idealized response element, shows how the EcRDBD, which has been previously reported to possess extraordinary flexibility, accommodates DNA-induced structural changes. Part of the C-terminal extension (CTE) of the EcRDBD folds into an α-helix whose location in the minor groove does not match any of the locations previously observed for nuclear receptors. Mutational analyses suggest that the α-helix is a component of EcR-box, a novel element indispensable for DNA-binding and located within the nuclear receptor CTE. This element seems to be a general feature of all known EcRs. |
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