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Structure paper

TitleStructural Basis for Gating and Activation of RyR1.
Journal, issue, pagesCell, Vol. 167, Issue 1, Page 145-157.e17, Year 2016
Publish dateSep 22, 2016
AuthorsAmédée des Georges / Oliver B Clarke / Ran Zalk / Qi Yuan / Kendall J Condon / Robert A Grassucci / Wayne A Hendrickson / Andrew R Marks / Joachim Frank /
PubMed AbstractThe type-1 ryanodine receptor (RyR1) is an intracellular calcium (Ca(2+)) release channel required for skeletal muscle contraction. Here, we present cryo-EM reconstructions of RyR1 in multiple ...The type-1 ryanodine receptor (RyR1) is an intracellular calcium (Ca(2+)) release channel required for skeletal muscle contraction. Here, we present cryo-EM reconstructions of RyR1 in multiple functional states revealing the structural basis of channel gating and ligand-dependent activation. Binding sites for the channel activators Ca(2+), ATP, and caffeine were identified at interdomain interfaces of the C-terminal domain. Either ATP or Ca(2+) alone induces conformational changes in the cytoplasmic assembly ("priming"), without pore dilation. In contrast, in the presence of all three activating ligands, high-resolution reconstructions of open and closed states of RyR1 were obtained from the same sample, enabling analyses of conformational changes associated with gating. Gating involves global conformational changes in the cytosolic assembly accompanied by local changes in the transmembrane domain, which include bending of the S6 transmembrane segment and consequent pore dilation, displacement, and deformation of the S4-S5 linker and conformational changes in the pseudo-voltage-sensor domain.
External linksCell / PubMed:27662087 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 6.6 Å
Structure data

EMDB-8342, PDB-5t15:
Structural basis for gating and activation of RyR1 (30 uM Ca2+ dataset, all particles)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-8372, PDB-5t9m:
Structure of rabbit RyR1 (Ca2+-only dataset, class 1)
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-8373, PDB-5t9n:
Structure of rabbit RyR1 (Ca2+-only dataset, class 2)
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-8374, PDB-5t9r:
Structure of rabbit RyR1 (Ca2+-only dataset, class 3)
Method: EM (single particle) / Resolution: 5.8 Å

EMDB-8375, PDB-5t9s:
Structure of rabbit RyR1 (Ca2+-only dataset, class 4)
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-8376, PDB-5t9v:
Structure of rabbit RyR1 (Caffeine/ATP/Ca2+ dataset, class 1)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-8377, PDB-5ta3:
Structure of rabbit RyR1 (Caffeine/ATP/Ca2+ dataset, class 2)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-8378, PDB-5tal:
Structure of rabbit RyR1 (Caffeine/ATP/Ca2+ dataset, class 1&2)
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-8379, PDB-5tam:
Structure of rabbit RyR1 (Caffeine/ATP/Ca2+ dataset, class 4)
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-8380, PDB-5tan:
Structure of rabbit RyR1 (Caffeine/ATP/Ca2+ dataset, class 3)
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-8381, PDB-5tap:
Structure of rabbit RyR1 (Caffeine/ATP/EGTA dataset, all particles)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-8382, PDB-5taq:
Structure of rabbit RyR1 (Caffeine/ATP/Ca2+ dataset, class 3&4)
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-8383, PDB-5tas:
Structure of rabbit RyR1 (Caffeine/ATP/EGTA dataset, class 1)
Method: EM (single particle) / Resolution: 6.2 Å

EMDB-8384, PDB-5tat:
Structure of rabbit RyR1 (Caffeine/ATP/EGTA dataset, class 2)
Method: EM (single particle) / Resolution: 4.8 Å

EMDB-8385, PDB-5tau:
Structure of rabbit RyR1 (Caffeine/ATP/EGTA dataset, class 3)
Method: EM (single particle) / Resolution: 6.2 Å

EMDB-8386, PDB-5tav:
Structure of rabbit RyR1 (Caffeine/ATP/EGTA dataset, class 4)
Method: EM (single particle) / Resolution: 4.8 Å

EMDB-8387, PDB-5taw:
Structure of rabbit RyR1 (ryanodine dataset, all particles)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-8388, PDB-5tax:
Structure of rabbit RyR1 (ryanodine dataset, class 1)
Method: EM (single particle) / Resolution: 6.6 Å

EMDB-8389, PDB-5tay:
Structure of rabbit RyR1 (ryanodine dataset, class 2)
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-8390, PDB-5taz:
Structure of rabbit RyR1 (ryanodine dataset, class 3)
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-8391, PDB-5tb0:
Structure of rabbit RyR1 (EGTA-only dataset, all particles)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-8392, PDB-5tb1:
Structure of rabbit RyR1 (EGTA-only dataset, class 1)
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-8393, PDB-5tb2:
Structure of rabbit RyR1 (EGTA-only dataset, class 2)
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-8394, PDB-5tb3:
Structure of rabbit RyR1 (EGTA-only dataset, class 3)
Method: EM (single particle) / Resolution: 4.7 Å

EMDB-8395, PDB-5tb4:
Structure of rabbit RyR1 (EGTA-only dataset, class 4)
Method: EM (single particle) / Resolution: 4.5 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-CA:
Unknown entry

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

ChemComp-CFF:
CAFFEINE / medication*YM

Source
  • homo sapiens (human)
  • oryctolagus cuniculus (rabbit)
  • Rabbit (rabbit)
KeywordsTRANSPORT PROTEIN/ISOMERASE / RyR / Ca2+ / EC coupling / gating / TRANSPORT PROTEIN-ISOMERASE complex

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