Research project Lipid Stabilisation and Modulation of Membrane Proteins
Membrane proteins are of exceptional importance for transport and signalling in the cell, and pumps and channels in particular are key examples of proteins that adopt different conformational states as part of cycles that define their function.
The complex environment makes it challenging to determine membrane protein structures, but advances in overexpression, purification and not least cryo-EM has led to a torrent of new structures in detergents or nanodiscs - in some cases even in alternative conformations. However, we are still largely treating the membrane as a passive solvent, while there is a huge amount of data showing how important the specific membrane environment is: Ligand-gated receptors responsible for nerve signal transmissions require cholesterol to work, polyunsaturated fatty acids have strong modulatory effects on voltage-gated channels, and cardiolipin influences function and dimerization of transporters - and yet we hardly know anything about lipid structural biology since the interactions are weaker and state-dependent. Here, we propose a cross-disciplinary research project with groups from Stockholm University, KTH, and Karolinska Institutet located at SciLifeLab to determine how specific lipids bind to and stabilise different states of membrane proteins and allosterically modulate functions, by using lipid-focused mass spectroscopy, functional assays in membranes with controlled lipid composition, cryo-EM, and not least molecular dynamics simulations.
Project members
Project managers
Erik Lindahl
Professor of Theoretical Chemistry
