Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Query: UMLS:C0018799 (
heart disease
)
34,133
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Intracellular Ca
2+
signalling processes are fundamental to muscle contraction, neurotransmitter release, cell growth and apoptosis. Release of Ca
2+
from the intracellular stores is supported by a series of ion channels in sarcoplasmic or endoplasmic reticulum (SR/ER). Among them, two isoforms of the trimeric intracellular cation (TRIC) channel family, named TRIC-A and
TRIC-B
, modulate the release of Ca
2+
through the ryanodine receptor or inositol triphosphate receptor, and maintain the homeostasis of ions within SR/ER lumen. Genetic ablations or mutations of TRIC channels are associated with hypertension,
heart disease
, respiratory defects and brittle bone disease. Despite the pivotal function of TRIC channels in Ca
2+
signalling, their pore architectures and gating mechanisms remain unknown. Here we present the structures of TRIC-B1 and TRIC-B2 channels from Caenorhabditis elegans in complex with endogenous phosphatidylinositol-4,5-biphosphate (PtdIns(4,5)P
2
, also known as PIP
2
) lipid molecules. The TRIC-B1/B2 proteins and PIP
2
assemble into a symmetrical homotrimeric complex. Each monomer contains an hourglass-shaped hydrophilic pore contained within a seven-transmembrane-helix domain. Structural and functional analyses unravel the central role of PIP
2
in stabilizing the cytoplasmic gate of the ion permeation pathway and reveal a marked Ca
2+
-induced conformational change in a cytoplasmic loop above the gate. A mechanistic model has been proposed to account for the complex gating mechanism of TRIC channels.
...
PMID:Pore architecture of TRIC channels and insights into their gating mechanism. 2769 20
