Activation of IP3 receptors requires an endogenous 1-8-14 calmodulin-binding motif.
| dc.creator | Sun, Yi | |
| dc.creator | Rossi, Ana M | |
| dc.creator | Rahman, Taufiq | |
| dc.creator | Taylor, Colin W | |
| dc.date | 2021-01-05T00:30:10Z | |
| dc.date | 2021-01-05T00:30:10Z | |
| dc.date | 2013-01-01 | |
| dc.date.accessioned | 2026-08-03T04:41:28Z | |
| dc.description | Binding of IP3 (inositol 1,4,5-trisphosphate) to the IP3-binding core (residues 224-604) of IP3Rs (IP3 receptors) initiates opening of these ubiquitous intracellular Ca2+ channels. The mechanisms are unresolved, but require conformational changes to pass through the suppressor domain (residues 1-223). A calmodulin-binding peptide derived from myosin light chain kinase uncouples these events. We identified a similar conserved 1-8-14 calmodulin-binding motif within the suppressor domain of IP3R1 and, using peptides and mutagenesis, we demonstrate that it is essential for IP3R activation, whether assessed by IP3-evoked Ca2+ release or patch-clamp recoding of nuclear IP3R. Mimetic peptides specifically inhibit activation of IP3R by uncoupling the IP3-binding core from the suppressor domain. Mutations of key hydrophobic residues within the endogenous 1-8-14 motif mimic the peptides. Our results show that an endogenous 1-8-14 motif mediates conformational changes that are essential for IP3R activation. The inhibitory effects of calmodulin and related proteins may result from disruption of this essential interaction. | |
| dc.format | ||
| dc.format | application/pdf | |
| dc.identifier | 0264-6021 | |
| dc.identifier | https://www.repository.cam.ac.uk/handle/1810/315666 | |
| dc.identifier | 10.17863/CAM.62780 | |
| dc.identifier | 1470-8728 | |
| dc.identifier.uri | https://repo.dare.co.zw/handle/123456789/192597 | |
| dc.language | eng | |
| dc.language | eng | |
| dc.publisher | Portland Press | |
| dc.publisher | https://doi.org/10.1042/bj20121034 | |
| dc.rights | Attribution 4.0 International | |
| dc.rights | https://creativecommons.org/licenses/by/4.0/ | |
| dc.subject | Amino Acid Motifs | |
| dc.subject | Amino Acid Sequence | |
| dc.subject | Animals | |
| dc.subject | Binding Sites | |
| dc.subject | Calmodulin | |
| dc.subject | Cattle | |
| dc.subject | Cell Line | |
| dc.subject | Inositol 1,4,5-Trisphosphate Receptors | |
| dc.subject | Molecular Sequence Data | |
| dc.subject | Protein Binding | |
| dc.subject | Protein Conformation | |
| dc.subject | Rats | |
| dc.title | Activation of IP3 receptors requires an endogenous 1-8-14 calmodulin-binding motif. | |
| dc.type | Article |