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DNA-binding mechanism of the monomeric orphan nuclear receptor NGFI-B

Abstract

The 2.7 Å X-ray crystal structure of the DNA-binding domain (DBD) of the orphan nuclear receptor, nerve growth factor-induced-B (NGFI-B), complexed to its high-affinity DNA target, represents the first structure analysis of a nuclear receptor DBD bound as a monomer to DNA. The structure of the core DBD and its interactions with the major groove of the DNA are similar to previously crystallographically solved DBD–DNA complexes in this superfamily; however, residues C-terminal to this core form a separate and unique substructure that interacts extensively and in a sequence-specific way with the minor groove of its DNA target, in particular with the characteristic 3 A-T base-pair identity element that extends 5' to the usual nuclear receptor half-site (AGGTCA).

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Figure 1: Sequences of the macromolecular components. Top panel shows domain structure of NGFI-B.
Figure 2: a, Overall structure of NGFI-B DBD on its high-affinity DNA target (RIBBONS39).
Figure 3: a, Stereo diagram of CTE of NGFI-B interacting with minor groove of its DNA target (RIBBONS39).
Figure 4: Sequence involved in CTE/minor-groove interactions in NGFI-B and SF-1 subfamilies.
Figure 5: Comparison of NGFI-B and RevErbα crystal structures.

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Acknowledgements

We thank T. Wilson and J. Milbrandt for providing the initial clone of NGFI-B, M. Capel for access to and help in the use of X12B beamline at NSLS, Brookhaven National Laboratory. Work at Yale was supported in part by a grant from the NIH. G.M. is a recipient of a NIH National Research Service Award.

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Correspondence to Paul B. Sigler.

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Meinke, G., Sigler, P. DNA-binding mechanism of the monomeric orphan nuclear receptor NGFI-B . Nat Struct Mol Biol 6, 471–477 (1999). https://doi.org/10.1038/8276

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