4tnt

Structure of the human mineralocorticoid receptor in complex with DNA

spinqualitylabelsall models 4tnt, resolution 2.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4tnt is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3938Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease MCR_HUMAN Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:177735. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment. Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:605115. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion. Function MCR_HUMAN Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels. Publication Abstract from PubMed The steroid hormone receptors regulate important physiological functions such as reproduction, metabolism, immunity, and electrolyte balance. Mutations within steroid receptors result in endocrine disorders and can often drive cancer formation and progression. Despite the conserved three-dimensional structure shared among members of the steroid receptor family and their overlapping DNA binding preference, activation of individual steroid receptors drive unique effects on gene expression. Here, we present the first structure of the human mineralocorticoid receptor DNA binding domain, in complex with a canonical DNA response element. The overall structure is similar to the glucocorticoid receptor DNA binding domain, but small changes in the mode of DNA binding and lever arm conformation may begin to explain the differential effects on gene regulation by the mineralocorticoid and glucocorticoid receptors. In addition, we explore the structural effects of mineralocorticoid receptor DNA binding domain mutations found in type I pseudohypoaldosteronism and multiple types of cancer. Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.,Hudson WH, Youn C, Ortlund EA PLoS One. 2014 Sep 4;9(9):e107000. doi: 10.1371/journal.pone.0107000. eCollection, 2014. PMID:25188500 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mineralocorticoid receptor

Proteopedia Page Contributors and Editors (what is this?)

OCA