AlbaNova Colloquium

Membrane proteins: at the interface between biophysics and molecular biology

by Gunnar von Heijne

Europe/Stockholm
Description

All living cells are surrounded by a thin lipid bilayer membrane that is impermeable to polar molecules and ions. Membrane-embedded proteins allow the cell to regulate the influx and efflux of small molecules/ions as well as macromolecules, and to react to the presence of signaling molecules in the external environment. Membrane proteins thus serve as the cell’s gatekeepers, and are absolutely essential to life. All-in-all, roughly 30% of the different proteins found in a typical organism are membrane proteins, despite the fact that they occupy only a small fraction of the total cell volume.

Having evolved to live happily in the apolar environment of a lipid bilayer, membrane proteins are designed according to different architectural principles than are water-soluble proteins. Moreover, the cell uses specialized “translocon” proteins to guide membrane proteins into the membrane as they are synthesized on the ribosome. Our main interest is to understand the molecular interactions that drive membrane protein insertion and folding by developing molecular biology techniques to measure physical parameters such as insertion free energies and forces acting on the nascent protein during the membrane insertion process in the living cell.

Place: Oskar Klein auditorium FR4.

https://stockholmuniversity.zoom.us/j/62663587311

A few relevant papers:

  1. 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) Molecular code for transmembrane-helix recognition by the Sec61 translocon. Nature 450, 1026-1030.
  2. Ismail, N., Hedman, R., Schiller, N., and von Heijne, G. (2012) A bi-phasic pulling force acts on transmembrane helices during translocon-mediated membrane integration. Nature Struct. Molec. Biol. 19, 1018-1023.
  3. Ismail, N., Hedman, R., Lindén, M., and von Heijne, G. (2015) Charge-driven dynamics of nascent chain movement through the SecYEG translocon. Nature Struct Molec Biol 22, 145-149.
  4. Öjemalm, K., Higuchi, T., Lara, P., Lindahl, E., Suga, H., and von Heijne, G. (2016) Energetics of side-chain snorkeling in transmembrane helices probed by non-proteinogenic amino acids. Proc Natl Acad Sci USA 113, 10559-10564.
  5. Niesen, M.J.M., Müller-Lucks, A., Hedman, R., von Heijne, G., and Miller III, T.F. (2018) Forces on nascent polypeptides during membrane insertion and translocation via the Sec translocon. Biophys J 115, 1885-1894. 
  6. Seurig, M., Ek, M., von Heijne, G., and Fluman, N. (2019) Dynamic membrane topology in an unassembled membrane protein. Nature Chem Biol 15, 945-948.
  7. Nicolaus, F., Metola, A., Mermans, D., Liljenström, A., Krč, A., Abdullahi, S.M.,  Matthew Zimmer4, Miller III, T.F., von Heijne, G. (2021) Residue-by-residue analysis of cotranslational membrane protein integration in vivo. eLife 10:e64302.