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Published Online January 25, 2007
Science DOI: 10.1126/science.1135406

Reports

Submitted on September 21, 2006
Accepted on January 16, 2007

Emulating Membrane Protein Evolution by Rational Design

Mikaela Rapp 1, Susanna Seppälä 1, Erik Granseth 2, Gunnar von Heijne 2*

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

* To whom correspondence should be addressed.
Gunnar von Heijne , E-mail: gunnar{at}dbb.su.se

How do integral membrane proteins evolve in size and complexity? Here, using the small multidrug-resistance protein EmrE from E. coli as a model, we experimentally demonstrate that the evolution of membrane proteins composed of two homologous but oppositely oriented domains can occur in a small number of steps, starting from an original 'dual topology' protein that evolves, via 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.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)