2A3I

Structural and Biochemical Mechanisms for the Specificity of Hormone Binding and Coactivator Assembly by Mineralocorticoid Receptor

Summary for 2A3I

• Entry DOI: 10.2210/pdb2a3i/pdb
• Descriptor: Mineralocorticoid receptor, Nuclear receptor coactivator 1, residues 1430-1441, CORTICOSTERONE, ... (4 entities in total)
• Functional Keywords: transcription factor, transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P08235; Nucleus : Q15788
• Total number of polymer chains: 2
• Total formula weight: 31236.22

Authors

Li, Y.,Suino, K.,Daugherty, J.,Xu, H.E. (deposition date: 2005-06-24, release date: 2005-07-19, Last modification date: 2024-02-14)

Primary citation

Li, Y.,Suino, K.,Daugherty, J.,Xu, H.E.
Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor
Mol.Cell, 19:367-380, 2005

PubMed Abstract: 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.

PubMed: 16061183
DOI: 10.1016/j.molcel.2005.06.026

Experimental method

X-RAY DIFFRACTION (1.95 Å)