Reversible binding of divalent cations to Ductin protein assemblies-A putative new regulatory mechanism of membrane traffic processes

Ductins are a family of homologous and structurally similar membrane proteins with 2 or 4 trans-membrane alpha-helices. The active forms of the Ductins are membranous ring- or star-shaped oligomeric assemblies and they provide various pore, channel, gap-junction functions, assist in membrane fusion processes and also serve as the rotor c-ring domain of V-and F-ATPases. All functions of the Ductins have been reported to be sensitive to the presence of certain divalent metal cations (Me2+), most frequently Cu2+ or Ca2+ ions, for most of the better known members of the family, and the mechanism of this effect is not yet known. Given that we have earlier found a prominent Me2+ binding site in a well-characterised Ductin protein, we hypothesise that certain divalent cations can structurally modulate the various functions of Ductin assemblies via affecting their stability by reversible non-covalent binding to them. A fine control of the stability of the assembly ranging from separated monomers through a loosely/weakly to tightly/strongly assembled ring might render precise regulation of Ductin functions possible. The putative role of direct binding of Me2+ to the c-ring subunit of active ATP hydrolase in autophagy and the mechanism of Ca2+-dependent formation of the mitochondrial permeability transition pore are also discussed.

Automated summary

Ductins are a family of membrane proteins that are structurally similar and have 2 or 4 trans-membrane alpha-helices. They have various functions including pore, channel, and gap-junction functions, as well as assisting in membrane fusion processes and serving as the rotor c-ring domain of V- and F-ATPases. The functions of Ductins are sensitive to the presence of certain divalent metal cations, and it is hypothesized that these cations can structurally modulate the functions of Ductin assemblies by reversible non-covalent binding to them. The direct binding of Me2+ to the c-ring subunit of active ATP hydrolase in autophagy and the mechanism of Ca2+-dependent formation of the mitochondrial permeability transition pore are also discussed.