A novel folding assay demonstrates that the T1 domain of voltage-gated K+ channels folds while still attached to membrane-bound ribosomes, providing a tool to diagnose assembly defects.
Advances Kv channel biogenesis models; leaves open applicability to human cardiac channelopathies.
Voltage-gated K(+) channels (Kv) are tetramers whose assembly is coordinated in part by a conserved T1 recognition domain. Although T1 achieves its quaternary structure in the ER, nothing is known about its acquisition of tertiary structure. We developed a new folding assay that relies on intramolecular cross-linking of pairs of cysteines engineered at the folded T1 monomer interface. Using this assay, we show directly that the T1 domain is largely folded while the Kv protein is still attached to membrane-bound ribosomes. The ER membrane facilitates both folding and oligomerization of Kv proteins. We show that folding and oligomerization assays can be used to study coupling between these two biogenic events and diagnose defects in assembly of Kv channels.
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Kosolapov et al. (2003) studied this question.
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