Activation of nuclear receptors: a perspective from structural genomics.
Crystal structures of more than two dozen different nuclear receptor ligand binding domains have defined a simple paradigm of receptor activation, in which agonist binding induces the activation function-2 (AF-2) helix to form a charge clamp for coactivator recruitment. Recent structural studies present a surprising contrast. Activation of the mouse LRH-1 receptor is independent of a bound agonist despite its large ligand binding pocket, whereas the activation of the Drosophila DHR38 receptor is dependent on ecdysteroids even though the receptor lacks a ligand binding pocket. These new findings shed light on the diverse structural mechanisms that nuclear receptors have evolved for activation, and have important implications in their respective signaling pathways.
Li
Yong
Y
Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USA.
Lambert
Millard H
MH
Xu
H Eric
HE
D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila; D023281:Genomics; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D018160:Receptors, Cytoplasmic and Nuclear