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

Authors

Jorg Balss, Technische Universität Darmstadt
Panagiotis Papatheodorou, Ruhr-Universitat Bochum
Mario Mehmel, Technische Universität Darmstadt
Dirk Baumeister, Technische Universität Darmstadt
Brigitte Hertel, Technische Universität Darmstadt
Nicolas Delaroque, Max Planck Institute of Chemical Ecology
Frank C. Chatelain, University of California - San Francisco
Daniel L. Minor Jr., University of California - San Francisco
James L. Van Etten, University of Nebraska - LincolnFollow
Joachim Rassow, Ruhr-Universitat Bochum
Anna Moroni, Universita degli Studi
Gerhard Thiel, Technische Universität DarmstadtFollow

Document Type

Article

Date of this Version

6-2008

Citation

PNAS, August 26, 2008, vol. 105, no. 34, pp.12313–12318.

Comments

© 2008 by The National Academy of Sciences of the USA. Used by permission.

Abstract

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 >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.