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Science 13 November 1992:
Vol. 258. no. 5085, pp. 1152 - 1155
DOI: 10.1126/science.1279807
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Articles

Science, Vol 258, Issue 5085, 1152-1155
Copyright © 1992 by American Association for the Advancement of Science

articles

A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels

L Heginbotham, T Abramson, and R MacKinnon

Department of Neurobiology, Harvard Medical School, Boston, MA 02115.

The overall sequence similarity between the voltage-activated K+ channels and cyclic nucleotide-gated ion channels from retinal and olfactory neurons suggests that they arose from a common ancestor. On the basis of sequence comparisons, mutations were introduced into the pore of a voltage-activated K+ channel. These mutations confer the essential features of ion conduction in the cyclic nucleotide-gated ion channels; the mutant K+ channels display little selectivity among monovalent cations and are blocked by divalent cations. The property of K+ selectivity is related to the presence of two amino acids that are absent from the pore-forming region of the cyclic nucleotide-gated channels. These data demonstrate that very small differences in the primary structure of an ion channel can account for extreme functional diversity, and they suggest a possible connection between the pore-forming regions of K+, Ca2+, and cyclic nucleotide-gated ion channels.


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P Hidalgo and R MacKinnon (1995)
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Calcium-Calmodulin Modulation of the Olfactory Cyclic Nucleotide-Gated Cation Channel.
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Two identical noninteracting sites in an ion channel revealed by proton transfer.
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