6MU1

Structure of full-length IP3R1 channel bound with Adenophostin A

Summary for 6MU1

• Entry DOI: 10.2210/pdb6mu1/pdb
• EMDB information: 9243 9244
• Descriptor: Inositol 1,4,5-trisphosphate receptor type 1, Adenophostin A (2 entities in total)
• Functional Keywords: inositol 1, 4, 5-trisphosphate receptor, calcium release channel, neuronal type 1, adenophostin a, membrane protein, ip3r-channel activator
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 4
• Total formula weight: 1252445.29

Authors

Serysheva, I.I.,Fan, G.,Baker, M.R.,Wang, Z.,Seryshev, A.,Ludtke, S.J.,Baker, M.L. (deposition date: 2018-10-22, release date: 2018-12-05, Last modification date: 2024-12-25)

Primary citation

Fan, G.,Baker, M.R.,Wang, Z.,Seryshev, A.B.,Ludtke, S.J.,Baker, M.L.,Serysheva, I.I.
Cryo-EM reveals ligand induced allostery underlying InsP3R channel gating.
Cell Res., 28:1158-1170, 2018

PubMed Abstract: Inositol-1,4,5-trisphosphate receptors (InsPRs) are cation channels that mobilize Ca from intracellular stores in response to a wide range of cellular stimuli. The paradigm of InsPR activation is the coupled interplay between binding of InsP and Ca that switches the ion conduction pathway between closed and open states to enable the passage of Ca 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 InsPR1 from rat cerebellum determined to 4.1 Å resolution in the presence of activating concentrations of Ca and adenophostin A (AdA), a structural mimetic of InsP and the most potent known agonist of the channel. Comparison with the 3.9 Å-resolution structure of InsPR1 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 InsPR channel.

PubMed: 30470765
DOI: 10.1038/s41422-018-0108-5

Experimental method

ELECTRON MICROSCOPY (4.1 Å)