2a3i
From Proteopedia
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Structural and Biochemical Mechanisms for the Specificity of Hormone Binding and Coactivator Assembly by Mineralocorticoid Receptor
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Overview
Mineralocorticoid receptor (MR) controls sodium homeostasis and blood, pressure through hormone binding and coactivator recruitment. Here, we, report a 1.95 A crystal structure of the MR ligand binding domain, containing a single C808S mutation bound to corticosterone and the fourth, LXXLL motif of steroid receptor coactivator-1 (SRC1-4). Through a, combination of biochemical and structural analyses, we demonstrate that, SRC1-4 is the most potent MR binding motif and mutations that disrupt the, MR/SRC1-4 interactions abolish the ability of the full-length SRC1 to, coactivate MR. The structure also reveals a compact steroid binding pocket, with a unique topology that is primarily defined by key residues of, helices 6 and 7. Mutations swapping a single residue at position 848 from, helix H7 between MR and glucocorticoid receptor (GR) switch their hormone, specificity. Together, these findings provide critical insights into the, molecular basis of hormone binding and coactivator recognition by MR and, related steroid receptors.
Disease
Known diseases associated with this structure: Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy OMIM:[600983], Pseudohypoaldosteronism type I, autosomal dominant OMIM:[600983]
About this Structure
2A3I is a Protein complex structure of sequences from Homo sapiens with C0R as ligand. Active as Histone acetyltransferase, with EC number 2.3.1.48 Full crystallographic information is available from OCA.
Reference
Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor., Li Y, Suino K, Daugherty J, Xu HE, Mol Cell. 2005 Aug 5;19(3):367-80. PMID:16061183
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