Distinct conformational states of nuclear receptor-bound CRSP-Med complexes.
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.
Taatjes
Dylan J
DJ
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley, California 94720, USA.
Schneider-Poetsch
Tilman
T
Tjian
Robert
R
D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D011487:Protein Conformation; D018167:Receptors, Calcitriol / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic
D001426:Bacterial Proteins; C117286:CRSP protein, human; D018167:Receptors, Calcitriol; D011988:Receptors, Thyroid Hormone; D015534:Trans-Activators