Senyon Choe and Paul Pfaffinger reply

Our primary concern in reporting any scientific finding is to be accurate and precise. In a Letter to Nature, there is the additional requirement of brevity, while making findings accessible to a general scientific readership. Regarding the source of the Shaker protein, we erred on the side of accuracy, precision and brevity, but lost a general scientific reader, such as Ashburner. The protein source was identified at several points in our Letter1 as the AKv1.1a Shaker-type potassium channel, and a reference to the first use of this name in the literature was provided. A query of NCBI GenBank with the name AKv1.1a correctly identifies the Aplysia californica channel sequence, and provides a page of further information.

A complete entry for our crystal structure was supplied to the Protein Data Bank, who were instructed to release this information upon publication. We believe that scientific advance thrives on openness, and we have an obligation to make available our material and data once published.

Finally, the use of the Shaker name to identify the channel subfamily, rather than a specific gene from Drosophila, is perhaps an important topic for further discussion. Because we entered into this problem from the viewpoint of trying to understand how the ordered assembly of potassium-channel subunits is restricted to heteromultimerization with other proteins in the same subfamily, we see the importance of the Shaker subfamily name. Indeed, from our viewpoint it is remarkable that Shaker subfamily members selectively heteromultimerize across species, from Aplysia to human, and probably even elephants and lesser-eared bats (although the molecular biology of ion channels in the latter species has been woefully neglected).

We have produced a comparative analysis of the structural conservation of the T1 domain region for all 55 sequences that we could clearly identify in the gene database as Shaker members, as implicitly provided in Fig. 3b of the Letter2. The complete alignment is accessible at: http://sbl.salk.edu/choe/clustal.html. We hope to provide further information about this topic, and other implications of our research on the T1 domain, for both Shaker and non-Shaker channels, in future reports.