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Distinct conformational states of nuclear receptor–bound CRSP–Med complexes

Nature Structural & Molecular Biology volume 11, pages 664–671 (2004)Cite this article

Abstract

The human CRSP–Med coactivator complex is targeted by a diverse array of sequence-specific regulatory proteins. Using EM and single-particle reconstruction techniques, we recently completed a structural analysis of CRSP–Med bound to VP16 and SREBP-1a. Notably, these activators induced distinct conformational states upon binding the coactivator. Ostensibly, these different conformational states result from VP16 and SREBP-1a targeting distinct subunits in the CRSP–Med complex. To test this, we conducted a structural analysis of CRSP–Med bound to either thyroid hormone receptor (TR) or vitamin D receptor (VDR), both of which interact with the same subunit (Med220) of CRSP–Med. Structural comparison of TR- and VDR-bound complexes (at a resolution of 29 Å) indeed reveals a shared conformational feature that is distinct from other known CRSP– Med structures. Importantly, this nuclear receptor–induced structural shift seems largely dependent on the movement of Med220 within the complex.

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Figure 1: TR and VDR bind two distinct mediator complexes: CRSP–Med and ARC-L–Med.
Figure 2: Subunit composition and transcriptional activity of TR- and VDR-CRSP–Med.
Figure 3: EM analysis of NR-bound CRSP–Med complexes.
Figure 4: NR-CRSP–Med structures have a shared conformational handedness that is different from other known CRSP–Med conformations.
Figure 5: Conformational change involves Med220.

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Acknowledgements

We thank E. Nogales for the use of her electron microscope and for helpful comments on the manuscript. We also thank C. Inouye for providing purified GTFs used for the in vitro transcription system. This work was funded by grants from the US National Institutes of Health and the Howard Hughes Medical Institute.

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Author notes

  1. Dylan J Taatjes

    Present address: Department of Chemistry and Biochemistry, University of Colorado, Campus Box 215, Boulder, Colorado, 80309, USA

Authors and Affiliations

  1. Department of Molecular and Cell Biology, Howard Hughes Medical Institute, 401 Barker Hall, University of California, Berkeley, 94720, California, USA

    Dylan J Taatjes, Tilman Schneider-Poetsch & Robert Tjian

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  1. Dylan J Taatjes
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Correspondence to Robert Tjian.

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Supplementary information

Supplementary Fig. 1

Purification scheme. (PDF 15 kb)

Supplementary Fig. 2

Angular distribution. (PDF 207 kb)

Supplementary Fig. 3

TR-ARC-L-Med structure. (PDF 59 kb)

Supplementary Fig. 4

TR and VDR alignment. (PDF 43 kb)

Supplementary Table 1

Correlation coefficients. (PDF 20 kb)

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Taatjes, D., Schneider-Poetsch, T. & Tjian, R. Distinct conformational states of nuclear receptor–bound CRSP–Med complexes. Nat Struct Mol Biol 11, 664–671 (2004). https://doi.org/10.1038/nsmb789

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