Conformational landscape and ligand-dependent clustering of the human type 2 IP 3 receptor (opens in new tab)

Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are tetrameric ER Ca2+ channels that shape intracellular Ca2+ signaling in response to IP3, regulating diverse physiological processes. The structural basis for subtype-specific regulation among the three subtypes (IP3R-1–3) remains incompletely understood due to the lack of IP3R-2 structures. Here, we report cryo-electron microscopy (cryo-EM) structures of human IP3R-2 in distinct conformations in the presence and absence of IP3, Ca2+, and...