2aa5 Citations

A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor.

J Biol Chem 280 31283-93 (2005)
Related entries: 2aa2, 2aa6, 2aa7, 2aax, 2ab2

Cited: 96 times
EuropePMC logo PMID: 15967794

Abstract

Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand. In addition, most activating ligands hydrogen bond to Thr945 on helix 10. Structural characterization of the naturally occurring S810L mutant explains how stabilization of a helix 3/helix 5 interaction can circumvent the requirement for this hydrogen bond network. Taken together, these results explain the potency of MR activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone.

Articles - 2aa5 mentioned but not cited (7)

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Reviews citing this publication (25)

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Articles citing this publication (64)

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