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Steroid receptor drugs have been available for more than half a century, but details of the ligand binding mechanism have remained elusive. We solved X-ray structures of the glucocorticoid and mineralocorticoid receptors to identify a conserved plasticity at the helix 6–7 region that extends the ligand binding pocket toward the receptor surface. Since none of the endogenous ligands exploit this region,...
Mesoderm development (MESD) is a 224 amino acid mouse protein that acts as a molecular chaperone for the low-density lipoprotein receptor (LDLR) family. Here, we provide evidence that the region 45–184 of MESD is essential and sufficient for this function and suggest a model for its mode of action. NMR studies reveal a β−α−β−β−α−β core domain with an α-helical N-terminal extension that interacts with...
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