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Originally published in Science Express on 25 January 2007
Science 2 March 2007:
Vol. 315. no. 5816, pp. 1282 - 1284
DOI: 10.1126/science.1135406
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Reports

Emulating Membrane Protein Evolution by Rational Design

Mikaela Rapp,1* Susanna Seppälä,1* Erik Granseth,1,2 Gunnar von Heijne1,2{dagger}

How do integral membrane proteins evolve in size and complexity? Using the small multidrug-resistance protein EmrE from Escherichia coli as a model, we experimentally demonstrated that the evolution of membrane proteins composed of two homologous but oppositely oriented domains can occur in a small number of steps: An original dual-topology protein evolves, through a gene-duplication event, to a heterodimer formed by two oppositely oriented monomers. This simple evolutionary pathway can explain the frequent occurrence of membrane proteins with an internal pseudo–two-fold symmetry axis in the plane of the membrane.

1 Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
2 Stockholm Bioinformatics Center, AlbaNova, SE-106 91 Stockholm, Sweden.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: gunnar{at}dbb.su.se

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