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 Angstrom) 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.