Long distance interactions within the potassium channel pore are revealed by molecular diversity of viral proteins

Sabrina Gazzarrini, Ming Kang, James L. Van Etten, Sascha Tayefeh, Stefan M. Kast, Dario DiFrancesco, Gerhard Thiel, Anna Moroni

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35 Scopus citations


Kcv is a 94-amino acid protein encoded by chlorella virus PBCV-1 that corresponds to the pore module of K+ channels. Therefore, Kcv can be a model for studying the protein design of K+ channel pores. We analyzed the molecular diversity generated by ∼1 billion years of evolution on kcv genes isolated from 40 additional chlorella viruses. Because the channel is apparently required for virus replication, the Kcv variants are all functional and contain multiple and dispersed substitutions that represent a repertoire of allowed sets of amino acid substitutions (from 4 to 12 amino acids). Correlations between amino acid substitutions and the new properties displayed by these channels guided site-directed mutations that revealed synergistic amino acid interactions within the protein as well as previously unknown interactions between distant channel domains. The effects of these multiple changes were not predictable from a priori structural knowledge of the channel pore.

Original languageEnglish (US)
Pages (from-to)28443-28449
Number of pages7
JournalJournal of Biological Chemistry
Issue number27
Publication statusPublished - Jul 2 2004


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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