Transmembrane domain

Receptor

Organic chemistry

Voltage-dependent calcium channel

TRPC3

Biology

Biophysics

TRPC6

Transient receptor potential channel

TRPC

Allosteric regulation

Calcium in biology

Chemistry

Calcium

Cell biology

Biochemistry

Intracellular

Calcium channel

Neuron

Guo et al. identified three intracellular calcium-binding sites (CBS) in the hTRPC3/6 channel: CBS1 is inhibitory and CBS3 is activating. Gain-of-function mutations of hTRPC6 impair the inhibitory CBS1 but retain the activating CBS3, resulting in the positive feedback of calcium signals in podocytes and, finally, leading to the disease FSGS.

Structural mechanism of human TRPC3 and TRPC6 channel regulation by their intracellular calcium-binding sites