Perspective: Assembly and Dynamics of Integral Membrane Proteins

Membrane proteins account for 25 – 30 % of a cell’s proteome and function as fusion factors, adhesion molecules, receptors, channels etc. Their membrane-spanning helices can induce dimerization or oligomerization, specific protein/lipid interactions, drive membrane fusion, catalyze lipid flip/flop, serve as substrates for intramembrane proteases etc.

Our mission:

To understand the mechanisms by which transmembrane domains (TMDs) self-interact, their conformational dynamics, and their ability to interact with surrounding lipids.

To elucidate the functional relevance of these interconnected structural properties.

Transmembrane helix-helix interactions

• Which types of amino acid interfaces can support TMD-TMD interactions?
• Which kinds of TMD-TMD interfaces were invented by nature?
• How have TMD-TMD interfaces evolved?
• Methods to measure TMD-TMD interactions

Transmembrane helix backbone dynamics

• How does primary structure define TMD backbone dynamics?
• Ways to measure backbone dynamics

Transmembrane helix/lipid interactions

• How are TMD / lipid interactions connected to TMD-TMD interactions and helix backbone dynamics?
• Methods to investigate TMD / lipid interactions

Functional implications of TMD-TMD interactions, TMD backbone dynamics, and TMD/lipid interactions in:

• membrane fusion by dedicated membrane proteins (SNAREs)
• catalyses of transbilayer movement of lipids (lipid flip/flop)
• intramembrane proteolysis by γ-secretase?

Instrumentation:

The lab hosts modern equipment to do experiments in molecular biology, biochemistry and biophysics.