Critical assessment of a proposed model of Shaker

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Abstract
Detailed three‐dimensional structures at atomic resolution are essential to understand how voltage‐activated K+ channels function. The X‐ray crystallographic structure of the KvAP channel has offered the first view at atomic resolution of the molecular architecture of a voltage‐activated K+ channel [Jiang et al. (2003) Nature 423, 33]. In the crystal, the voltage sensors are bound by monoclonal Fab fragments, which apparently induce a non‐native conformation of the tetrameric channel. Thus, despite this significant advance our knowledge of the native conformation of a Kv channel in a membrane remains incomplete. Numerous results from different experimental approaches provide very specific constraints on the structure of K+ channels in functional conformations. These results can be used to go further in trying to picture the native conformation of voltage‐gated K+ channels. However, the direct translation of all the available information into three‐dimensional models is not straightforward and many questions about the structure of voltage‐activated K+ channels are still unanswered. Our aim in this review is to summarize the most important pieces of information currently available and to provide a critical assessment of the model of Shaker recently proposed by Lainé et al. [Neuron 39 (2003) 467].