The Cysteine-rich Secretory Protein Domain of Tpx-1 Is Related to Ion Channel Toxins and Regulates Ryanodine Receptor Ca2+ Signaling

摘要: Abstract The cysteine-rich secretory proteins (Crisp) are predominantly found in the mammalian male reproductive tract as well venom of reptiles. Crisps two domain with a structurally similar yet evolutionary diverse N-terminal and characteristic C-terminal domain, which we refer to Crisp domain. We presented NMR solution structure mouse Tpx-1, showed that it contains subdomains, one has fold ion channel regulators BgK ShK. Furthermore, have demonstrated for first time regulatory activity is attributed Specifically, Tpx-1 inhibited cardiac ryanodine receptor (RyR) 2 an IC50 between 0.5 1.0 μm activated skeletal RyR1 AC50 1 10 when added cytoplasmic receptor. This was nonvoltage-dependent weakly voltage-dependent, respectively. both RyR forms at negative bilayer potentials no effect positive luminal These data show on its own can regulate provide compelling evidence role regulation Ca2+ fluxes observed during sperm capacitation.