Structural insights into the regulatory mechanism of inositol 1,4,5-trisphosphate receptor.
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Structural insights into the regulatory mechanism of inositol 1,4,5-trisphosphate receptor.

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In a variety of cells Ca2+ signaling processes such as Ca2+ oscillation are mediated by the ER membrane-associated Ca2+ release channel, inositol 1,4,5-trisphosphate receptor (IP3R). IP3R plays a vital role in the control of cellular and physiological processes as diverse as cell division, cell proliferation, apoptosis, fertilization, development, behavior, memory and learning. Opening of the Ca2+ release channel requires sequential binding of two intracellular messengers IP3 and Ca2+. I have determined the crystal structure of the receptor IP3-binding core in complex with IP3. The structure consists of two asymmetric domains, one with the beta-trefoil fold and the other possessing an "armadillo-like" repeats. The cleft formed by the two domains exposes a cluster of arginine and lysine residues that coordinate the three phosphoryl groups of IP 3. Putative Ca2+ binding sites are identified in two separate locations within the IP3-binding core. More recently I determined the crystal structure of the IP3 binding suppression domain, which includes the first 220 residues directly preceding the IP 3-binding core domain. The conserved surface on one side of the suppressor domain appears to interact with the IP3-binding core domain. Interestingly, this surface is in close proximity to the previously proposed binding sites of Homer, RACK1, calmodulin, and CaBP1. Structural information for the IP 3R N-terminus sheds light onto the mechanism underlying the receptor"s sensitivity to the IP3 molecule and its communication with cellular signaling proteins.

The Physical Object
Pagination180 leaves.
Number of Pages180
ID Numbers
Open LibraryOL21302884M
ISBN 10049407731X

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  Inositol 1,4,5-trisphosphate receptors (IP 3 R) are intracellular Ca 2+ release channels whose opening requires binding of two intracellular messengers IP 3 and Ca 2+.The regulation of IP 3 R function has also been shown to involve a variety of cellular proteins. Recent biochemical and structural analyses have deepened our understanding of how the IP 3-operated Ca 2+ channel by: Inositol 1,4,5-trisphosphate (IP3) receptor up-regulation in hypertension is associated with sensitization of Ca 2+ release and vascular smooth muscle Structural insights into the regulatory mechanism of IP3 receptor. The ligand binding site and transduction mechanism in the inositol-1,4,5-triphosphate receptor. EMBO J. 9 – Cited by: 7.   Three-dimensional structure of the type 1 inositol 1,4,5-trisphosphate receptor at 24 Å resolution. EMBO J. 21, – () CAS Article Google ScholarCited by: Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca 2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis, fertilization, development, behavior, learning and memory.

Abstract. Activation of cells by many extracellular agonists leads to the production of inositol 1,4,5-trisphosphate (IP 3).IP 3 is a global messenger that easily diffuses in the cytosol. Its receptor (IP 3 R) is a Ca 2+-release channel located on intracellular membranes, especially the endoplasmic reticulum (ER).The IP 3 R has an affinity for IP 3 in the low nanomolar range. The inositol 1,4,5 trisphosphate (IP) receptor (IPR) is a Ca release channel that responds to the second messenger IP. Exquisite modulation of intracellular Ca release via IPRs is achieved by the ability of IPR to integrate signals from numerous small molecules and proteins including nucleotides, kinases, and phosphatases, as well as nonenzyme proteins. Because the ion conduction pore composes.   Phosphatidylinositol 4,5-bisphosphate (PIP2), a plasma membrane lipid, is hydrolyzed by Gq-protein–coupled receptor (GqPCR) signaling into inositol 1,4,5-trisphosphate and diacylglycerol—extensively studied second messengers with profound regulatory effects in the vasculature. However, there is extensive evidence that PIP2 directly regulates ion channels, a finding . Ligand recognition and regulatory mechanisms of inositol 1,4,5-trisphosphate receptor. 21, Ames J.B. and Ikura M. Structure and membrane-targeting mechanism of retinal Ca2+-binding proteins, recoverin and GCAP

Inositol 1,4,5-trisphosphate receptors (IP 3Rs) are a family of intracellular ion channels that mediate cal-cium (Ca2+) release from the endoplasmic reticulum (ER) following stimulation by the second messenger inositol 1,4,5-trisphosphate (IP 3). Generation of IP 3 molecules is caused by the activation of phospholipase.   The inositol 1,4,5-trisphosphate (IP 3) receptor (IP 3 R) is a universal intracellular Ca 2+-release is activated after cell stimulation and plays a crucial role in the initiation and propagation of the complex spatio-temporal Ca 2+ signals that control cellular processes as different as fertilization, cell division, cell migration, differentiation, metabolism, muscle contraction. The type II inositol 1,4,5-trisphosphate receptor can trigger Ca2+ waves in rat hepatocytes. Gastroenterology (4): , PMID: Hirota J, Furuichi T and Mikoshiba K. Inositol 1,4,5-trisphosphate receptor type 1 is a substrate for caspase-3 and is cleaved during apoptosis in a caspasedependent manner.   I. Overview. A wide range of cytosolic factors regulate the activity of the three members of the inositol 1,4,5-trisphosphate receptor (IP 3 R) family (IP 3 R1, IP 3 R2, IP 3 R3; Patel et al., , Patterson et al., ).IP 3 and Ca 2+ are the primary activators of the receptors whereas phosphorylation events, nucleotides, and protein-binding partners are important allosteric modulators .