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Nat Struct Mol Biol. 2004 Jul;11(7):664-71. Epub 2004 Jun 13.

Distinct conformational states of nuclear receptor-bound CRSP-Med complexes.

Author information

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

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 A) 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.

PMID:
15195149
DOI:
10.1038/nsmb789
[Indexed for MEDLINE]

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