Characterization of a cytosolic and a luminal Ca2+ binding site in the type I inositol 1,4,5-trisphosphate receptor - PubMed (original) (raw)
. 1996 Oct 25;271(43):27005-12.
doi: 10.1074/jbc.271.43.27005.
Affiliations
- PMID: 8900188
- DOI: 10.1074/jbc.271.43.27005
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Characterization of a cytosolic and a luminal Ca2+ binding site in the type I inositol 1,4,5-trisphosphate receptor
I Sienaert et al. J Biol Chem. 1996.
Free article
Abstract
To study the Ca2+ regulation of the inositol 1,4,5-trisphosphate receptor (InsP3R) at the molecular level, we expressed various cytosolic and luminal regions of the mouse type I InsP3R as glutathione S-transferase fusion proteins. 45Ca2+ and ruthenium red overlay studies and Stains-all spectra and staining revealed both a cytosolic and a luminal Ca2+ binding site. The luminal Ca2+ binding site was mapped to the nonconserved acidic subregion of the luminal loop between amino acids 2463 and 2528. A K0.5 of 0.3 microM and a Hill coefficient of 1.1 were determined by 45Ca2+ overlay by quantification of 45Ca2+ binding on blots. The cytosolic Ca2+ binding site was localized in a region just preceding the transmembrane domain M1. The Ca2+ binding was mapped to a 23-amino acid stretch between amino acids 2124 and 2146. This cytosolic region showed a single high affinity site for Ca2+, with a K0.5 of 0. 8 microM and a Hill coefficient of 1.0. Neither of the identified Ca2+ binding regions contained an EF-hand motif. We conclude that the type I InsP3R has at least two quite distinct types of Ca2+ binding sites, which are localized in different structural regions of the protein.
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