SPring-8, the large synchrotron radiation facility

Electrical signals play critical roles in heart beating, sensation, memory and metabolism. Voltage-gated ion channels are key proteins that function in cellular membranes for electrical signals. Hv1 (VSOP) is the unique ion channel protein that was discovered in Japan. It has a voltage-sensor domain (VSD) with dual roles of voltage sensing and proton permeation. Its gating of proton conduction pathway is sensitive to pH gradient and extracellular Zn²⁺. We succeeded to solve a crystal structure of mouse Hv1 in the resting state at 3.45 Å resolution. The structure showed a ‘closed Wagasa (Japanese umbrella)’ shape with a long helix running through the cell membrane to the cytoplasm and featured a wide inner-accessible vestibule. Voltage sensing amino acids on the protein were located below the phenylalanine-containing “gascket” region in the center of membrane, indicating that structure was in resting state. The extracellular region of each protomer coordinated a Zn²⁺, which is rich in seminal fluid to suppress sperm motility before ejaculation. These findings provide a platform for understanding the general principles of electrical signals in neuron and muscle, and pH homeostasis in blood cells.

Publication:
"X-ray crystal structure of voltage-gated proton channel"
Takeshita, K., Sakata, S., Yamashita, E., Fujiwara, Y., Kawanabe, A., Kurokawa,T., Okochi, Y., Matsuda, M., Narita, H., Okamura, Y., Nakagawa, A.
Nature Structural & Molecular Biology, Published online 02 March 2014