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

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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
Volume279
Issue number27
DOIs
StatePublished - Jul 2 2004

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Potassium Channels
Viral Proteins
Chlorella
Amino Acid Substitution
Amino Acids
Viruses
Substitution reactions
Virus Replication
Proteins
Mutation
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Long distance interactions within the potassium channel pore are revealed by molecular diversity of viral proteins. / Gazzarrini, Sabrina; Kang, Ming; Van Etten, James L.; Tayefeh, Sascha; Kast, Stefan M.; DiFrancesco, Dario; Thiel, Gerhard; Moroni, Anna.

In: Journal of Biological Chemistry, Vol. 279, No. 27, 02.07.2004, p. 28443-28449.

Research output: Contribution to journalArticle

Gazzarrini, Sabrina ; Kang, Ming ; Van Etten, James L. ; Tayefeh, Sascha ; Kast, Stefan M. ; DiFrancesco, Dario ; Thiel, Gerhard ; Moroni, Anna. / Long distance interactions within the potassium channel pore are revealed by molecular diversity of viral proteins. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 27. pp. 28443-28449.
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