6jg3 | pdb_00006jg3

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

Loading... Status: waiting for Mol* initialization Structural highlights 6jg3 is a 4 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The type 2 ryanodine receptor (RyR2) is responsible for releasing Ca(2+) 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(2+) 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(2+) 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(2+) 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. Molecular basis for allosteric regulation of the type 2 ryanodine receptor channel gating by key modulators.,Chi X, Gong D, Ren K, Zhou G, Huang G, Lei J, Zhou Q, Yan N Proc Natl Acad Sci U S A. 2019 Dec 2. pii: 1914451116. doi:, 10.1073/pnas.1914451116. PMID:31792195 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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