Research Project:
Membrane protein assembly and structure.
Address:
E-mail: gunnar@dbb.su.se
Phone: (+46)-8-16 2590
Fax: (+46)-8-15 3679
Research group
Joanna Slusky, Morten Nørholm, Susanna Seppälä, Marie Österberg, Salomé Botelho, Karin Geiger, Pilar Lloris, Carmen Galian, Katrin Halling, Patrik Björkholm.
Project description
Membrane proteins serve a number of very important functions in both prokaryotic and eukaryotic cells. They are built according to structural principles different from those of globular proteins. A full understanding of membrane proteins requires a conceptual framework where processes of protein translocation across membranes and the physical chemistry of lipid-protein interactions play major roles.
We have a long-standing interest in problems related to membrane protein assembly and structure. Work in our lab has pointed to the central importance of positively charged amino acids as determinants of membrane protein topology, has led to the development of new theoretical methods for predicting transmembrane segments, and has illuminated many aspects of membrane protein assembly in both prokaryotic and eukaryotic cells. Ongoing theoretical and experimental work is directed towards both the topology and 3D structure of membrane proteins.
Recent papers
Kauko, A., Hedin, L., Thebaud, E., Cristobal, S., Elofsson, A., and von Heijne, G. (2010) Repositioning of transmembrane a-helices during membrane protein folding. J.Mol.Biol. 397, 190-201
Sakata, S., Kurokawa, T., Nørholm, M.H.H., Takagi, M., Okochi, Y., von Heijne, G., and Okamura, Y. (2010) Activities of the voltage-gated proton channel truncated in S4. Proc.Natl.Acad.Sci. USA, 107, 2313-2318.
Hessa, T., Reithinger, J.H., von Heijne, G., and Kim, H. (2009) Quantitative analysis of transmembrane helix integration in the endoplasmic reticulum in S. cerevisiae. J.Mol.Biol. 386, 1222-1228.
Jaud, S., Fernández-Vidal, M., Nilsson, I.M., Meindl-Beinker, N.M., Hübner, N., Tobias, D.J., von Heijne, G., and White, S.H. (2009) Insertion of short transmembrane helices by the Sec61 translocon. Proc.Natl.Acad.Sci. USA 106, 11588-11593
Lundin, C., Kim, H., Nilsson, IM., White, S.H., and von Heijne, G. (2008) The molecular code for protein insertion in the ER membrane is similar for Nin-Cout and Nout-Cin transmembrane helices. Proc.Natl.Acad.Sci. USA, 105, 15702-15707
Bernsel, A., Viklund, H., Falk, J., Lindahl, E., von Heijne, G., and Elofsson, A. (2008) Prediction of membrane-protein topology from first principles. Proc.Natl.Acad.Sci. USA 105, 7177-7181.
Hessa, T., Meindl-Beinker, N.M., Bernsel, A., Kim, H., Sato, Y., Lerch-Bader, M., Nilsson, IM., White, S.H., and von Heijne, G. (2007) The molecular code for transmembrane-helix recognition by the ER translocon. Nature 450, 1026-1030.
Rapp, M., Seppälä, S., Granseth, E., and von Heijne, G. (2007) Emulating membrane protein evolution by rational design. Science 315, 1282-1284.
Rapp, M., Seppälä, S., Granseth, E., and von Heijne, G. (2006) Identification and evolution of dual topology membrane proteins. Nature Struct.Mol.Biol. 13, 112-116.
Kim, H., Melén, K., Österberg, M., and von Heijne, G. (2006) A global topology map of the Saccharomyces cerevisiae membrane proteome. Proc.Natl.Acad.Sci. USA 103, 11142- 11147
Daley, D.O., Rapp, M., Granseth, E., Melén, K., Drew, D., and von Heijne, G. (2005) Global topology analysis of the Escherichia coli inner membrane proteome. Science 308, 1321-1323.
Hessa, T., Kim., H., Bihlmaier, K., Lundin, C., Boekel, J., Andersson, H., Nilsson, I.M., White, S.H., and von Heijne, G. (2005) Recognition of transmembrane helices by the endoplasmic reticulum translocon. Nature 433, 377-381.
Hessa, T., White, S.H., and von Heijne, G. (2005) Membrane insertion of a potassium channel voltage sensor. Science 307, 1427.
Drew, D., Sjöstrand, D., Nilsson, J., Urbig, T., Chin, C., de Gier, J-W., and von Heijne, G. (2002) Rapid topology mapping of E. coli inner membrane proteins by prediction and PhoA/GFP fusion analysis. Proc.Natl.Acad.Sci.USA 99, 2690-2695.
Full publication list, see http://www.sbc.su.se/gunnar/gvhpub.html
Acknowledgments
The group is supported by grants from the European Research Council, the Swedish Research Council, the Swedish Cancer Foundation, the Foundation for Strategic Research, the European Community, the Human Frontiers Science Program, and the National Institutes of Health.