| Structural highlights
Function
[ITPR1_MOUSE] Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5-trisphosphate. Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Binding of inositol 1,4,5-trisphosphate (IP(3)) to the amino-terminal region of IP(3) receptor promotes Ca(2+) release from the endoplasmic reticulum. Within the amino terminus, the first 220 residues directly preceding the IP(3) binding core domain play a key role in IP(3) binding suppression and regulatory protein interaction. Here we present a crystal structure of the suppressor domain of the mouse type 1 IP(3) receptor at 1.8 A. Displaying a shape akin to a hammer, the suppressor region contains a Head subdomain forming the beta-trefoil fold and an Arm subdomain possessing a helix-turn-helix structure. The conserved region on the Head subdomain appeared to interact with the IP(3) binding core domain and is in close proximity to the previously proposed binding sites of Homer, RACK1, calmodulin, and CaBP1. The present study sheds light onto the mechanism underlying the receptor's sensitivity to the ligand and its communication with cellular signaling proteins.
Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor.,Bosanac I, Yamazaki H, Matsu-Ura T, Michikawa T, Mikoshiba K, Ikura M Mol Cell. 2005 Jan 21;17(2):193-203. PMID:15664189[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Furuichi T, Yoshikawa S, Miyawaki A, Wada K, Maeda N, Mikoshiba K. Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400. Nature. 1989 Nov 2;342(6245):32-8. PMID:2554142 doi:http://dx.doi.org/10.1038/342032a0
- ↑ Li G, Mongillo M, Chin KT, Harding H, Ron D, Marks AR, Tabas I. Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J Cell Biol. 2009 Sep 21;186(6):783-92. doi: 10.1083/jcb.200904060. Epub 2009 Sep, 14. PMID:19752026 doi:http://dx.doi.org/10.1083/jcb.200904060
- ↑ Yamazaki H, Chan J, Ikura M, Michikawa T, Mikoshiba K. Tyr-167/Trp-168 in type 1/3 inositol 1,4,5-trisphosphate receptor mediates functional coupling between ligand binding and channel opening. J Biol Chem. 2010 Nov 12;285(46):36081-91. doi: 10.1074/jbc.M110.140129. Epub, 2010 Sep 2. PMID:20813840 doi:http://dx.doi.org/10.1074/jbc.M110.140129
- ↑ Bosanac I, Yamazaki H, Matsu-Ura T, Michikawa T, Mikoshiba K, Ikura M. Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor. Mol Cell. 2005 Jan 21;17(2):193-203. PMID:15664189 doi:10.1016/j.molcel.2004.11.047
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