Professor Fei Sun’s laboratory studies the structure and function of membrane proteins and macromolecular complexes using cryo-electron microscopy, three-dimensional reconstruction and X-ray crystallography. Their work on the human voltage-gated proton channel Hv1 has recently been published in the Journal of Biological Chemistry1.

Voltage-gated proton channel (Hv channel) currents can be detected in many mammalian cells, including blood cells, such as macrophages, neutrophils, and eosinophils. Hv channels are responsible for the proton-transporting pathway which regulates intracellular pH during “respiratory burst” – the oxygen consumption associated with phagocytosis. They are activated by depolarization and intracellular acidification. Hv channels not only regulate pH in the cytoplasm but also provide protons in the phagosome, a closed membrane compartment where pathogens are killed and digested.

The voltage-gated proton channel Hv1 has a voltage sensordomain but lacks a pore domain. Although the C-terminal domainof Hv1 is known to be responsible for the dimeric architecture of thechannel, its role and structure are not known. Li et al. report that full-length Hv1 is mainly localized in the membranes of intracellular compartments rather than in the plasma membrane. Truncation ofeither theNorCterminus alone, or both together,showed that deletion of theN-terminal did not alter localization, but deletion of theCterminus, either alone or together with the N terminus, resulted inexpression throughout the cell. These results indicate that the Cterminus is essential forHv1localization while theNterminus is not essential. Inthe 2.0 ？ structure of the C-terminal domain, the two monomersform a dimer via a parallela-helical coiled-coil, in which one chlorideion binds with theNhatom of Arg264.ApH-dependent structuralchange in the protein can be observed, but it remains adimer irrespective of pH.

1. Shu Jie Li, Qing Zhao, Qiangjun Zhou, Hideaki Unno, Yujia Zhai, and Fei Sun (2010) The Role and Structure of the Carboxyl-terminal Domain of the Human Voltage-gated Proton Channel Hv1. Journal of Biological Chemistry 285 (16): 12047–12054.

A Cl- ion near the Nh atom of Arg264 of one monomer of the dimer, in which the backbone of the dimeric coiled-coil structure is depicted as a ribbon with all side chains.