scholarly journals Identification of 70 calcium-sensing receptor mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular domain mutations at calcium-binding sites

2012 ◽  
Vol 21 (12) ◽  
pp. 2768-2778 ◽  
Author(s):  
F. M. Hannan ◽  
M. A. Nesbit ◽  
C. Zhang ◽  
T. Cranston ◽  
A. J. Curley ◽  
...  
Keyword(s):  
Binding Sites ◽  
Calcium Binding ◽  
Extracellular Domain ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Calcium Binding Sites

scholarly journals Mutation of the high affinity calcium binding sites in cardiac troponin C.

1992 ◽  
Vol 267 (2) ◽  
pp. 825-831 ◽  
Author(s):  
J C Negele ◽  
D G Dotson ◽  
W Liu ◽  
H L Sweeney ◽  
J A Putkey
Keyword(s):  
Binding Sites ◽  
Calcium Binding ◽  
Cardiac Troponin ◽  
Troponin C ◽  
High Affinity ◽  
Cardiac Troponin C ◽  
Calcium Binding Sites

Rat GTP cyclohydrolase I is a homodecameric protein complex containing high-affinity calcium-binding sites 1 1Edited by W. Baumeister

1998 ◽  
Vol 279 (1) ◽  
pp. 189-199 ◽  
Author(s):  
Michel O Steinmetz ◽  
Christoph Plüss ◽  
Urs Christen ◽  
Bettina Wolpensinger ◽  
Ariel Lustig ◽  
...  
Keyword(s):  
Protein Complex ◽  
Binding Sites ◽  
Calcium Binding ◽  
Gtp Cyclohydrolase I ◽  
Gtp Cyclohydrolase ◽  
High Affinity ◽  
Calcium Binding Sites

scholarly journals Characterization of the calcium-binding sites of calcineurin B

FEBS Letters ◽  
1995 ◽  
Vol 362 (1) ◽  
pp. 55-58 ◽  
Author(s):  
Lazaros T Kakalis ◽  
Michael Kennedy ◽  
Robert Sikkink ◽  
Frank Rusnak ◽  
Ian M Armitage
Keyword(s):  
Binding Sites ◽  
Calcium Binding ◽  
Calcineurin B ◽  
Calcium Binding Sites

Therapeutic Opportunities of Targeting Allosteric Binding Sites on the Calcium-Sensing Receptor

2021 ◽  
Vol 4 (2) ◽  
pp. 666-679
Author(s):  
Jiayin Diao ◽  
Aaron DeBono ◽  
Tracy M. Josephs ◽  
Jane E. Bourke ◽  
Ben Capuano ◽  
...  
Keyword(s):  
Binding Sites ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Allosteric Binding Sites

Peptide Blocking Self-Polymerization of Extracellular Calcium-Sensing Receptor Attenuates Hypoxia-Induced Pulmonary Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Rui Xiao ◽  
Shengquan Luo ◽  
Ting Zhang ◽  
Yankai Lv ◽  
Tao Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Disulfide Bonds ◽  
Acute Hypoxia ◽  
Extracellular Domain ◽  
Left Ventricular ◽  
Extracellular Calcium ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

Activation of the CaSR (extracellular calcium-sensing receptor) has been recognized as a critical mediator of hypoxia-induced pulmonary hypertension. Preventive targeting of the early initiating phase as well as downstream events after CaSR activation remains unexplored. As a representative of the G protein-coupled receptor family, CaSR polymerizes on cell surface upon stimulation. Immunoblotting together with MAL-PEG technique identified a reactive oxygen species-sensitive CaSR polymerization through its extracellular domain in pulmonary artery smooth muscle cells upon exposure to acute hypoxia. Fluorescence resonance energy transfer screening employing blocking peptides determined that cycteine129/131 residues in the extracellular domain of CaSR formed intermolecular disulfide bonds to promote CaSR polymerization. The monitoring of intracellular Ca 2+ signal highlighted the pivotal role of CaSR polymerization in its activation. In contrast, the blockade of disulfide bonds formation using a peptide decreased both CaSR and hypoxia-induced mitogenic factor expression as well as other hypoxic-related genes in vitro and in vivo and attenuated pulmonary hypertension development in rats. The blocking peptide did not affect systemic arterial oxygenation in vivo but inhibited acute hypoxia-induced pulmonary vasoconstriction. Pharmacokinetic analyses revealed a more efficient lung delivery of peptide by inhaled nebulizer compared to intravenous injection. In addition, the blocking peptide did not affect systemic arterial pressure, body weight, left ventricular function, liver, or kidney function or plasma Ca 2+ level. In conclusion, a peptide blocking CaSR polymerization reduces its hypoxia-induced activation and downstream events leading to pulmonary hypertension and represents an attractive inhaled preventive alternative worthy of further development.

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