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TitleStructural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca/ATP.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 1936, Year 2025
Publish dateFeb 24, 2025
AuthorsRisheng Wei / Qiang Chen / Lei Zhang / Congcong Liu / Chuang Liu / Chang-Cheng Yin / Hongli Hu /
PubMed AbstractThe type-1 ryanodine receptor (RyR1) is an intracellular calcium release channel for skeletal muscle excitation-contraction coupling. Previous structural studies showed that the RyR1 activity is ...The type-1 ryanodine receptor (RyR1) is an intracellular calcium release channel for skeletal muscle excitation-contraction coupling. Previous structural studies showed that the RyR1 activity is modulated by the exogenous regulators including caffeine, ryanodine, PCB-95 and diamide. An additional transmembrane helix, located adjacent to S1 and S4, has been observed in some structures, although its function remains unclear. Here, we report that using a mild purification procedure, this helix is co-purified with RyR1 and is designated as S0. When RyR1 is coupled with S0, it can be activated by Ca to an open state; however when decoupled from S0, it remains in primed state. S0 regulates the channel conformation by directly affecting the TM domain via the pVSD-S0-S4/S5 linker coupling, which facilitates the dilation of S6. Our results demonstrate that S0 is an essential component of RyR1 and plays a key role in the physiological regulation of RyR1 channel gating.
External linksNat Commun / PubMed:39994184 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 4.2 Å
Structure data

38042

8x48

EMDB-38042, PDB-8x48:
Cryo-EM structure of Ryanodine receptor 1 (EGTA)
Method: EM (single particle) / Resolution: 4.0 Å

38043

8x49

EMDB-38043, PDB-8x49:
Cryo-EM structure of Ryanodine receptor 1 (100 nM Ca2+)
Method: EM (single particle) / Resolution: 3.4 Å

38044

8x4a

EMDB-38044, PDB-8x4a:
Cryo-EM structure of Ryanodine receptor 1 (TM helix S0,100 nM Ca2+, closed state)
Method: EM (single particle) / Resolution: 3.8 Å

38045

8x4b

EMDB-38045, PDB-8x4b:
Cryo-EM structure of Ryanodine receptor 1 (TM helix S0,100 nM Ca2+, open state)
Method: EM (single particle) / Resolution: 4.2 Å

38046

8x4c

EMDB-38046, PDB-8x4c:
Cryo-EM structure of Ryanodine receptor 1 (20 uM Ca2+, 2 mM ATP)
Method: EM (single particle) / Resolution: 3.8 Å

38047

8x4d

EMDB-38047, PDB-8x4d:
Cryo-EM structure of Ryanodine receptor 1 (TM helix S0,20 uM Ca2+, 2 mM ATP)
Method: EM (single particle) / Resolution: 3.9 Å

38048

8x4e

EMDB-38048, PDB-8x4e:
Cryo-EM structure of Ryanodine receptor 1 (TM helix S0, 5 mM Ca2+)
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

Source
  • oryctolagus cuniculus (rabbit)
KeywordsMEMBRANE PROTEIN / Ryanodine Receptor / Calcium release channel

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