6JG3

Cryo-EM structure of RyR2 (Ca2+ alone dataset)

This is a non-PDB format compatible entry.

Summary for 6JG3

• Entry DOI: 10.2210/pdb6jg3/pdb
• EMDB information: 9823
• Descriptor: Ryanodine receptor 2, ZINC ION (2 entities in total)
• Functional Keywords: membrane protein
• Biological source: Sus scrofa
• Total number of polymer chains: 4
• Total formula weight: 2259884.14

Authors

Chi, X.M.,Gong, D.S.,Ren, K.,Zhou, G.W.,Huang, G.X.Y.,Lei, J.L.,Zhou, Q.,Yan, N. (deposition date: 2019-02-13, release date: 2019-12-11, Last modification date: 2024-03-27)

Primary citation

Chi, X.,Gong, D.,Ren, K.,Zhou, G.,Huang, G.,Lei, J.,Zhou, Q.,Yan, N.
Molecular basis for allosteric regulation of the type 2 ryanodine receptor channel gating by key modulators.
Proc.Natl.Acad.Sci.USA, 116:25575-25582, 2019

PubMed Abstract: The type 2 ryanodine receptor (RyR2) is responsible for releasing Ca from the sarcoplasmic reticulum of cardiomyocytes, subsequently leading to muscle contraction. Here, we report 4 cryo-electron microscopy (cryo-EM) structures of porcine RyR2 bound to distinct modulators that, together with our published structures, provide mechanistic insight into RyR2 regulation. Ca alone induces a contraction of the central domain that facilitates the dilation of the S6 bundle but is insufficient to open the pore. The small-molecule agonist PCB95 helps Ca to overcome the barrier for opening. FKBP12.6 induces a relaxation of the central domain that decouples it from the S6 bundle, stabilizing RyR2 in a closed state even in the presence of Ca and PCB95. Although the channel is open when PCB95 is replaced by caffeine and adenosine 5'-triphosphate (ATP), neither of the modulators alone can sufficiently counter the antagonistic effect to open the channel. Our study marks an important step toward mechanistic understanding of the sophisticated regulation of this key channel whose aberrant activity engenders life-threatening cardiac disorders.

PubMed: 31792195
DOI: 10.1073/pnas.1914451116

Experimental method

ELECTRON MICROSCOPY (6.1 Å)