Source:http://linkedlifedata.com/resource/pubmed/id/21876165
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
37
|
pubmed:dateCreated |
2011-9-14
|
pubmed:abstractText |
The inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) is an intracellular Ca(2+) release channel, and its opening is controlled by IP(3) and Ca(2+). A single IP(3) binding site and multiple Ca(2+) binding sites exist on single subunits, but the precise nature of the interplay between these two ligands in regulating biphasic dependence of channel activity on cytosolic Ca(2+) is unknown. In this study, we visualized conformational changes in IP(3)R evoked by various concentrations of ligands by using the FRET between two fluorescent proteins fused to the N terminus of individual subunits. IP(3) and Ca(2+) have opposite effects on the FRET signal change, but the combined effect of these ligands is not a simple summative response. The bell-shaped Ca(2+) dependence of FRET efficiency was observed after the subtraction of the component corresponding to the FRET change evoked by Ca(2+) alone from the FRET changes evoked by both ligands together. A mutant IP(3)R containing a single amino acid substitution at K508, which is critical for IP(3) binding, did not exhibit this bell-shaped Ca(2+) dependence of the subtracted FRET efficiency. Mutation at E2100, which is known as a Ca(2+) sensor, resulted in ?10-fold reduction in the Ca(2+) dependence of the subtracted signal. These results suggest that the subtracted FRET signal reflects IP(3)R activity. We propose a five-state model, which implements a dual-ligand competition response without complex allosteric regulation of Ca(2+) binding affinity, as the mechanism underlying the IP(3)-dependent regulation of the bell-shaped relationship between the IP(3)R activity and cytosolic Ca(2+).
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/enhanced cyan fluorescent protein,
http://linkedlifedata.com/resource/pubmed/chemical/yellow fluorescent protein, Bacteria
|
pubmed:status |
MEDLINE
|
pubmed:month |
Sep
|
pubmed:issn |
1091-6490
|
pubmed:author |
pubmed-author:EnomotoMasahiroM,
pubmed-author:GotoJun-IchiJ,
pubmed-author:IwaiMiwakoM,
pubmed-author:Matsu-uraToruT,
pubmed-author:MichikawaTakayukiT,
pubmed-author:MikoshibaKatsuhikoK,
pubmed-author:MiyamotoAkitoshiA,
pubmed-author:ShinoharaTadashiT,
pubmed-author:SuzukiAkioA,
pubmed-author:YamazakiHarukaH
|
pubmed:issnType |
Electronic
|
pubmed:day |
13
|
pubmed:volume |
108
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
15486-91
|
pubmed:meshHeading |
pubmed-meshheading:21876165-Animals,
pubmed-meshheading:21876165-Bacterial Proteins,
pubmed-meshheading:21876165-Calcium,
pubmed-meshheading:21876165-Cytosol,
pubmed-meshheading:21876165-Fluorescence Resonance Energy Transfer,
pubmed-meshheading:21876165-Green Fluorescent Proteins,
pubmed-meshheading:21876165-HeLa Cells,
pubmed-meshheading:21876165-Humans,
pubmed-meshheading:21876165-Inositol 1,4,5-Trisphosphate Receptors,
pubmed-meshheading:21876165-Ion Channel Gating,
pubmed-meshheading:21876165-Ligands,
pubmed-meshheading:21876165-Luminescent Proteins,
pubmed-meshheading:21876165-Mice,
pubmed-meshheading:21876165-Models, Biological,
pubmed-meshheading:21876165-Recombinant Fusion Proteins
|
pubmed:year |
2011
|
pubmed:articleTitle |
Mechanistic basis of bell-shaped dependence of inositol 1,4,5-trisphosphate receptor gating on cytosolic calcium.
|
pubmed:affiliation |
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|