6mu2 | pdb_00006mu2

Structure of full-length IP3R1 channel in the Apo-state

spinqualitylabelsall models 6mu2, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6mu2 is a 4 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ITPR1_RAT] 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 (By similarity). Publication Abstract from PubMed Inositol-1,4,5-trisphosphate receptors (InsP3Rs) are cation channels that mobilize Ca(2+) from intracellular stores in response to a wide range of cellular stimuli. The paradigm of InsP3R activation is the coupled interplay between binding of InsP3 and Ca(2+) that switches the ion conduction pathway between closed and open states to enable the passage of Ca(2+) through the channel. However, the molecular mechanism of how the receptor senses and decodes ligand-binding signals into gating motion remains unknown. Here, we present the electron cryo-microscopy structure of InsP3R1 from rat cerebellum determined to 4.1 A resolution in the presence of activating concentrations of Ca(2+) and adenophostin A (AdA), a structural mimetic of InsP3 and the most potent known agonist of the channel. Comparison with the 3.9 A-resolution structure of InsP3R1 in the Apo-state, also reported herein, reveals the binding arrangement of AdA in the tetrameric channel assembly and striking ligand-induced conformational rearrangements within cytoplasmic domains coupled to the dilation of a hydrophobic constriction at the gate. Together, our results provide critical insights into the mechanistic principles by which ligand-binding allosterically gates InsP3R channel. Cryo-EM reveals ligand induced allostery underlying InsP3R channel gating.,Fan G, Baker MR, Wang Z, Seryshev AB, Ludtke SJ, Baker ML, Serysheva II Cell Res. 2018 Nov 23. pii: 10.1038/s41422-018-0108-5. doi:, 10.1038/s41422-018-0108-5. PMID:30470765 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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