9YKK

Human type 2 IP3 receptor in apo state

This is a non-PDB format compatible entry.

Summary for 9YKK

• Entry DOI: 10.2210/pdb9ykk/pdb
• EMDB information: 73054
• Descriptor: Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2, ZINC ION (2 entities in total)
• Functional Keywords: inositol 1, 4, 5-triphosphate, ip3, receptor, calcium channel, type-2, ip3r, ip3r-2, itpr2, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 1259225.01

Authors

Liu, C.,Lan, Y.,Tang, Q.,Karakas, E. (deposition date: 2025-10-07, release date: 2026-07-01)

Primary citation

Liu, C.,Lan, Y.J.,Kushner, M.G.,Tang, Q.,Karakas, E.
Conformational landscape and ligand-dependent clustering of the human type 2 IP 3 receptor.
Nat Commun, 2026

PubMed Abstract: Inositol 1,4,5-trisphosphate (IP) receptors (IPRs) are tetrameric ER Ca channels that shape intracellular Ca signaling in response to IP, regulating diverse physiological processes. The structural basis for subtype-specific regulation among the three subtypes (IPR-1-3) remains incompletely understood due to the lack of IPR-2 structures. Here, we report cryo-electron microscopy (cryo-EM) structures of human IPR-2 in distinct conformations in the presence and absence of IP, Ca, and ATP. These structures define the conformational landscape of IPR-2, delineate ligand-binding interactions, and reveal shared architectural features alongside isoform-specific differences. We also resolve ligand-dependent IPR-2 assemblies, identifying a conformation-dependent inter-channel interface. Live-cell imaging demonstrates that IPR-2 undergoes clustering following ligand-induced Ca release, and disruption of this interface selectively abolishes clustering without impairing channel activity. Together, these findings provide a structural framework for human IPR-2 and establish a mechanism linking ligand-dependent conformational changes to inter-channel interactions and post-activation cellular clustering.

PubMed: 42315508
DOI: 10.1038/s41467-026-74494-y

Experimental method

ELECTRON MICROSCOPY (2.95 Å)