Science (American Association for the Advancement of Science), 2000-07, Vol.289 (5476), p.119-123
2000
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Details
- Autor(en) / Beteiligte
- Titel
- Activating Mineralocorticoid Receptor Mutation in Hypertension Exacerbated by Pregnancy
- Ist Teil von
- Science (American Association for the Advancement of Science), 2000-07, Vol.289 (5476), p.119-123
- Ort / Verlag
- Washington, DC: American Society for the Advancement of Science
- Erscheinungsjahr
- 2000
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5-helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.289.5476.119Titel-ID: cdi_proquest_miscellaneous_743656687
- Format
- –
- Schlagworte
- Adolescent, Aldosterone - metabolism, Amino Acid Sequence, Amino Acid Substitution, Amino acids, Base Sequence, Binding, Competitive, Biological and medical sciences, Blood pressure, Causes of, COS cells, Dimerization, Diseases of mother, fetus and pregnancy, Female, Genetic mutation, Gestational hypertension, Gynecology. Andrology. Obstetrics, Heterozygote, Humans, Hypertension, Hypertension - etiology, Hypertension - genetics, Hypertension - metabolism, Hypertension in pregnancy, Male, Medical research, Medical sciences, mineralcorticoid receptors, Models, Molecular, Molecular Sequence Data, Mutation, nuclear homrmone receptors, Nuclear receptors, Pedigree, Plasmids, Point Mutation, Preeclampsia, Pregnancy, Pregnancy Complications, Cardiovascular - etiology, Pregnancy Complications, Cardiovascular - metabolism, Pregnancy. Fetus. Placenta, Progesterone - metabolism, Protein Conformation, Protein Structure, Secondary, Receptors, Receptors, Mineralocorticoid - chemistry, Receptors, Mineralocorticoid - genetics, Receptors, Mineralocorticoid - metabolism, Receptors, Steroid - chemistry, Receptors, Steroid - metabolism, Steroids, Steroids - metabolism