8TKF

Human Type 3 IP3 Receptor - Activated State (+IP3/ATP/JD Ca2+)

これはPDB形式変換不可エントリーです。

8TKF の概要

• エントリーDOI: 10.2210/pdb8tkf/pdb
• EMDBエントリー: 41349
• 分子名称: Inositol 1,4,5-trisphosphate receptor type 3, ZINC ION, D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE, ... (7 entities in total)
• 機能のキーワード: ion channel, calcium channel, endoplasmic reticulum, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 1238868.10

構造登録者

Paknejad, N.,Sapuru, V.,Hite, R.K. (登録日: 2023-07-25, 公開日: 2023-11-08, 最終更新日: 2024-10-30)

主引用文献

Paknejad, N.,Sapuru, V.,Hite, R.K.
Structural titration reveals Ca 2+ -dependent conformational landscape of the IP 3 receptor.
Nat Commun, 14:6897-6897, 2023

PubMed Abstract: Inositol 1,4,5-trisphosphate receptors (IPRs) are endoplasmic reticulum Ca channels whose biphasic dependence on cytosolic Ca gives rise to Ca oscillations that regulate fertilization, cell division and cell death. Despite the critical roles of IPR-mediated Ca responses, the structural underpinnings of the biphasic Ca dependence that underlies Ca oscillations are incompletely understood. Here, we collect cryo-EM images of an IPR with Ca concentrations spanning five orders of magnitude. Unbiased image analysis reveals that Ca binding does not explicitly induce conformational changes but rather biases a complex conformational landscape consisting of resting, preactivated, activated, and inhibited states. Using particle counts as a proxy for relative conformational free energy, we demonstrate that Ca binding at a high-affinity site allows IPRs to activate by escaping a low-energy resting state through an ensemble of preactivated states. At high Ca concentrations, IPRs preferentially enter an inhibited state stabilized by a second, low-affinity Ca binding site. Together, these studies provide a mechanistic basis for the biphasic Ca-dependence of IPR channel activity.

PubMed: 37898605
DOI: 10.1038/s41467-023-42707-3

実験手法

ELECTRON MICROSCOPY (3.2 Å)