Carboxy-terminal domain mediates assembly of the voltage-gated rat ether-a-go-go potassium channel

The specific assembly of subunits to oligomers is an important prerequisite for producing functional potassium channels, We have studied the assembly of voltage-gated rat ether-a-go-go (r-eag) potassium channels with two complementary assays, In protein overlay binding experiments it was shown that a 41-amino-acid domain, close to the r-eag subunit carboxy-terminus, is important for r-eag subunit interaction, In an in vitro expression system it was demonstrated that r-eag subunits lacking this assembly domain cannot form functional potassium channels, Also, a similar to 10-fold molar excess of the r-eag carboxy-terminus inhibited in coexpression experiments the formation of functional r-eag channels, When the r-eag carboxy-terminal assembly domain had been mutated, the dominant-negative effect of the r-eag carboxy-terminus on r-eag channel expression was abolished, The results demonstrate that a carboxy-terminal assembly domain is essential for functional r-eag potassium channel expression, in contrast to the one of Shaker-related potassium channels, which is directed by an amino-terminal assembly domain.