9ymz

Human type 2 IP3 receptor in the inactive-like state (IP3/ATP)

spinqualitylabelsall models 9ymz, resolution 3.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ymz is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.14Å Ligands: ATP, I3P, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ITPR2_HUMAN Isolated generalized anhidrosis with normal sweat glands. The disease is caused by variants affecting the gene represented in this entry. Function ITPR2_HUMAN Inositol 1,4,5-trisphosphate-gated calcium channel that upon inositol 1,4,5-trisphosphate binding transports calcium from the endoplasmic reticulum lumen to cytoplasm. Exists in two states; a long-lived closed state where the channel is essentially 'parked' with only very rare visits to an open state and that ligands facilitate the transition from the 'parked' state into a 'drive' mode represented by periods of bursting activity (By similarity).[UniProtKB:Q9Z329] Publication Abstract from PubMed Inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) are tetrameric ER Ca(2+) channels that shape intracellular Ca(2+) signaling in response to IP(3), regulating diverse physiological processes. The structural basis for subtype-specific regulation among the three subtypes (IP(3)R-1-3) remains incompletely understood due to the lack of IP(3)R-2 structures. Here, we report cryo-electron microscopy (cryo-EM) structures of human IP(3)R-2 in distinct conformations in the presence and absence of IP(3), Ca(2+), and ATP. These structures define the conformational landscape of IP(3)R-2, delineate ligand-binding interactions, and reveal shared architectural features alongside isoform-specific differences. We also resolve ligand-dependent IP(3)R-2 assemblies, identifying a conformation-dependent inter-channel interface. Live-cell imaging demonstrates that IP(3)R-2 undergoes clustering following ligand-induced Ca(2+) release, and disruption of this interface selectively abolishes clustering without impairing channel activity. Together, these findings provide a structural framework for human IP(3)R-2 and establish a mechanism linking ligand-dependent conformational changes to inter-channel interactions and post-activation cellular clustering. Conformational landscape and ligand-dependent clustering of the human type 2 IP(3) receptor.,Liu C, Lan YJ, Kushner MG, Tang Q, Karakas E Nat Commun. 2026 Jun 19. doi: 10.1038/s41467-026-74494-y. PMID:42315508 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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