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Identification and evolution of dual-topology membrane proteins

Nature Structural & Molecular Biology volume 13, pages 112–116 (2006)Cite this article

Abstract

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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Figure 1: Dual-topology membrane proteins.
Figure 2: Charge mutations shift the orientations of dual-topology membrane proteins.
Figure 3: Homologs of dual-topology proteins occur as closely spaced gene pairs with opposite predicted orientations or as singletons with predicted dual topology.
Figure 4: An internally duplicated protein (Staphylococcus aureus BAB56779) in the DUF606 family.

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Acknowledgements

This work was supported by grants from the Swedish Foundation for Strategic Research, the Swedish Research Council, the Swedish Cancer Foundation, the Marianne and Marcus Wallenberg Foundation and the European Commission (BioSapiens) to G.v.H.

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Author notes

  1. Mikaela Rapp and Erik Granseth: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Center for Biomembrane Research, AlbaNova, Stockholm University, Stockholm, SE-10691, Sweden

    Mikaela Rapp, Susanna Seppälä & Gunnar von Heijne

  2. Stockholm Bioinformatics Center, AlbaNova, Stockholm University, Stockholm, SE-10691, Sweden

    Erik Granseth & Gunnar von Heijne

Authors
  1. Mikaela Rapp
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  4. Gunnar von Heijne
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Corresponding author

Correspondence to Gunnar von Heijne.

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Supplementary information

Supplementary Table 1

The 174 genome sequences used in the Pfam-based searches for homologs to the E. coli proteins analysed in the main paper. (PDF 94 kb)

Supplementary Table 2

Homologs to the different protein families found in the Pfam searches. (PDF 1575 kb)

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Rapp, M., Granseth, E., Seppälä, S. et al. Identification and evolution of dual-topology membrane proteins. Nat Struct Mol Biol 13, 112–116 (2006). https://doi.org/10.1038/nsmb1057

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