Nature Structural & Molecular Biology 13, 112 - 116 (2006)
Published online: 22 January 2006; | doi:10.1038/nsmb1057
Identification and evolution of dual-topology membrane proteinsMikaela Rapp1, 3, Erik Granseth2, 3, Susanna Seppälä1
& Gunnar von Heijne1, 21
Center for Biomembrane Research, Department of Biochemistry and Biophysics, AlbaNova, Stockholm University, SE-10691 Stockholm, Sweden. 2
Stockholm Bioinformatics Center, AlbaNova, Stockholm University, SE-10691 Stockholm, Sweden. 3
These authors contributed equally to this work.
Correspondence should be addressed to Gunnar von Heijne gunnar@dbb.su.se Integral membrane proteins are generally believed to have unique membrane topologies. However, it has been suggested that dual-topology proteins that adopt a mixture of two opposite orientations in the membrane may exist. Here we show that the membrane orientations of five dual-topology candidates identified in Escherichia coli are highly sensitive to changes in the distribution of positively charged residues, that genes in families containing dual-topology candidates occur in genomes either as pairs or as singletons and that gene pairs encode two oppositely oriented proteins whereas singletons encode dual-topology candidates. Our results provide strong support for the existence of dual-topology proteins and shed new light on the evolution of membrane-protein topology and structure.
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