Determination of the endothelin-1 recognition sites of endothelin receptor type A by the directed-degeneration method

Han, Seong Gu; Ko, Sanghwan; Lee, Won Kyu; Jung, Sang Taek; Yu, Yeon Gyu

doi:10.1038/s41598-017-08096-6

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…Based on this circumstance and the high overall sequence similarity of 62% between both receptor subtypes, it can be expected that the identified ET B R structures can serve as ideal templates to build ET A R homology-models. This is supported by experimental studies providing overlapping amino acids relevant for peptide-ligand binding ( 87 ). However, elucidation of potential differences in ligand binding properties ( 88 ), such as ligand affinity, definitely requires the determination of ET A R structures and structural complexes.…”

Section: Receptor Structures With Bound Agonistsmentioning

confidence: 81%

Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting

et al. 2022

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In conjunction with the endothelin (ET) type A (ETAR) and type B (ETBR) receptors, angiotensin (AT) type 1 (AT1R) and type 2 (AT2R) receptors, are peptide-binding class A G-protein-coupled receptors (GPCRs) acting in a physiologically overlapping context. Angiotensin receptors (ATRs) are involved in regulating cell proliferation, as well as cardiovascular, renal, neurological, and endothelial functions. They are important therapeutic targets for several diseases or pathological conditions, such as hypertrophy, vascular inflammation, atherosclerosis, angiogenesis, and cancer. Endothelin receptors (ETRs) are expressed primarily in blood vessels, but also in the central nervous system or epithelial cells. They regulate blood pressure and cardiovascular homeostasis. Pathogenic conditions associated with ETR dysfunctions include cancer and pulmonary hypertension. While both receptor groups are activated by their respective peptide agonists, pathogenic autoantibodies (auto-Abs) can also activate the AT1R and ETAR accompanied by respective clinical conditions. To date, the exact mechanisms and differences in binding and receptor-activation mediated by auto-Abs as opposed to endogenous ligands are not well understood. Further, several questions regarding signaling regulation in these receptors remain open. In the last decade, several receptor structures in the apo- and ligand-bound states were determined with protein X-ray crystallography using conventional synchrotrons or X-ray Free-Electron Lasers (XFEL). These inactive and active complexes provide detailed information on ligand binding, signal induction or inhibition, as well as signal transduction, which is fundamental for understanding properties of different activity states. They are also supportive in the development of pharmacological strategies against dysfunctions at the receptors or in the associated signaling axis. Here, we summarize current structural information for the AT1R, AT2R, and ETBR to provide an improved molecular understanding.

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Section: Receptor Structures With Bound Agonistsmentioning

confidence: 81%

Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting

et al. 2022

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“…It is upregulated by mechanical stretch ( 46 ) and hypoxia ( 47 ), and plasma ET-1 is elevated in preeclampsia and gestational hypertension ( 48 , 49 ). It exerts its effects by binding G-protein coupled receptors on vascular smooth muscle cells and endothelial cells ( 50 ), a byproduct of which may be intracellular lipid accumulation ( 51 , 52 ). Thus, ET-1 may be a common trigger for lipid accumulation within endothelial cells in acute atherosis and in hepatocytes in the associated rare disease, acute fatty liver of pregnancy ( 44 ).…”

Section: Acute Atherosis Etiologymentioning

confidence: 99%

Acute Atherosis Lesions at the Fetal-Maternal Border: Current Knowledge and Implications for Maternal Cardiovascular Health

et al. 2021

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Decidua basalis, the endometrium of pregnancy, is an important interface between maternal and fetal tissues, made up of both maternal and fetal cells. Acute atherosis is a uteroplacental spiral artery lesion. These patchy arterial wall lesions containing foam cells are predominantly found in the decidua basalis, at the tips of the maternal arteries, where they feed into the placental intervillous space. Acute atherosis is prevalent in preeclampsia and other obstetric syndromes such as fetal growth restriction. Causal factors and effects of acute atherosis remain uncertain. This is in part because decidua basalis is challenging to sample systematically and in large amounts following delivery. We summarize our decidua basalis vacuum suction method, which facilitates tissue-based studies of acute atherosis. We also describe our evidence-based research definition of acute atherosis. Here, we comprehensively review the existing literature on acute atherosis, its underlying mechanisms and possible short- and long-term effects. We propose that multiple pathways leading to decidual vascular inflammation may promote acute atherosis formation, with or without poor spiral artery remodeling and/or preeclampsia. These include maternal alloreactivity, ischemia-reperfusion injury, preexisting systemic inflammation, and microbial infection. The concept of acute atherosis as an inflammatory lesion is not novel. The lesions themselves have an inflammatory phenotype and resemble other arterial lesions of more extensively studied etiology. We discuss findings of concurrently dysregulated proteins involved in immune regulation and cardiovascular function in women with acute atherosis. We also propose a novel hypothesis linking cellular fetal microchimerism, which is prevalent in women with preeclampsia, with acute atherosis in pregnancy and future cardiovascular and neurovascular disease. Finally, women with a history of preeclampsia have an increased risk of premature cardiovascular disease. We review whether presence of acute atherosis may identify women at especially high risk for premature cardiovascular disease.

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Use of a Poly‐γ‐Glutamic Acid‐Derived Amphipathic Polypeptide for the Reconstitution of Membrane Proteins

Han

Choi

Kim

et al. 2020

Bulletin Korean Chem Soc

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Determination of the endothelin-1 recognition sites of endothelin receptor type A by the directed-degeneration method

Cited by 4 publications

References 38 publications

Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting

Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting

Acute Atherosis Lesions at the Fetal-Maternal Border: Current Knowledge and Implications for Maternal Cardiovascular Health

Use of a Poly‐γ‐Glutamic Acid‐Derived Amphipathic Polypeptide for the Reconstitution of Membrane Proteins

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