Fig. 8: Model for activation and opening of RyR1 by multiple atorvastatin molecules. | Nature Communications

Fig. 8: Model for activation and opening of RyR1 by multiple atorvastatin molecules.

From: Cryo-electron microscopy reveals sequential binding and activation of Ryanodine Receptors by statin triplets

Fig. 8

Binding of one atorvastatin (yellow) per protomer is observed with a small increase in the cleft between the pVSD (containing helices S1–S4) and the pore-forming region of a neighboring subunit (S5’–S6’). This is accomplished by a small shift of S5’ and the S4–S5 linker helix. This binding primes the channel for binding of two additional atorvastatins (green and magenta), whereby the S4 helix shifts relative to the S1–S3 helices, along with an additional large shift in the S4–S5 linker helix, and a widening of the pore by movement of the S6 helices.

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