Albumin is a common soluble protein with many physiological roles, including hormone transport, antioxidant activity, and regulation of cellular pressure and intracellular pH. Zhao et al. found that albumin binding is needed for the activation of the human voltage-gated protein channel (hHv1). Binding and mutagenesis analyses and modeling by molecular dynamics simulation showed that albumin binds across the two voltage sensor domains of hHV1 to enhance the open-state probability of the channel and increase the proton current. In the uterus, high albumin levels promote binding to the hHv1 channel to initiate sperm capacitation. Albumin likely has similar stimulatory activities on the hHv1 channel in other tissues, for example, in sustaining pathological levels of reactive oxygen species and proteases from neutrophils in some disease states.
Nat. Commun. 12, 3855 (2021).
