Key result
Kv1.3 subunits assemble primarily through a dimerization of dimers using distinct interaction sites.
The study provides evidence that voltage-gated K+ channels assemble via a dimerization of dimers pathway rather than sequential monomer addition.
Advances Kv1.3 biogenesis insights; leaves open whether assembly pathway informs channel-targeted cardiovascular therapies.
Voltage-gated K+ channels are tetrameric, but how the four subunits assemble is not known. We analyzed inactivation kinetics and peak current levels elicited for a variety of wild-type and mutant Kv1.3 subunits, expressed singly, in combination, and as tandem constructs, to show that 1) the dominant pathway involves a dimerization of dimers, and 2) dimer-dimer interaction may involve interaction sites that differ from those involved in monomer-monomer association. Moreover, using nondenaturing gel electrophoresis, we detected dimers and tetramers, but not trimers, in the translation reaction of Kv1.3 monomers.
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Tu et al. (1999) studied this question. Wild-type and mutant Kv1.3 subunits was evaluated on Inactivation kinetics and peak current levels to determine assembly pathway. Analysis of Kv1.3 subunits demonstrated that the dominant channel assembly pathway involves a dimerization of dimers, with distinct interaction sites for dimer-dimer versus monomer-monomer association.
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