Transmembrane domain length of viral K+ channels is a signal for mitochondria targeting

Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12313-8. doi: 10.1073/pnas.0805709105. Epub 2008 Aug 21.


K(+) channels operate in the plasma membrane and in membranes of organelles including mitochondria. The mechanisms and topogenic information for their differential synthesis and targeting is unknown. This article describes 2 similar viral K(+) channels that are differentially sorted; one protein (Kesv) is imported by the Tom complex into the mitochondria, the other (Kcv) to the plasma membrane. By creating chimeras we discovered that mitochondrial sorting of Kesv depends on a hierarchical combination of N- and C-terminal signals. Crucial is the length of the second transmembrane domain; extending its C terminus by > or = 2 hydrophobic amino acids redirects Kesv from the mitochondrial to the plasma membrane. Activity of Kesv in the plasma membrane is detected electrically or by yeast rescue assays only after this shift in sorting. Hence only minor structural alterations in a transmembrane domain are sufficient to switch sorting of a K(+) channel between the plasma membrane and mitochondria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Cell Membrane / metabolism
  • Humans
  • Membrane Proteins
  • Mitochondria / metabolism*
  • Mutagenesis, Site-Directed
  • Phycodnaviridae / chemistry
  • Potassium Channels / chemistry
  • Potassium Channels / metabolism*
  • Protein Sorting Signals*
  • Protein Transport
  • Saccharomyces cerevisiae / genetics
  • Transfection
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*


  • Membrane Proteins
  • Potassium Channels
  • Protein Sorting Signals
  • Viral Proteins