Aggregation of Integral Proteins

(supported by the Austrian Science Fund, DOC 130 doc.funds BioMolStruc)

start of project: 01. 10. 2021
end of project: 30. 09. 2025

We hypothesize that the stored membrane curvature strain gives a significant contribution to the aggregation of transmembrane proteins in addition to other membrane-mediated mechanisms (hydrophobic mismatch, overall membrane curvature, etc.)  and specific lipid-protein interactions. Previously, we calculated that the intrinsic lipid curvature leads to the aggregation of proteins of different shapes in specific lipid environments, such as e.g. cholesterol enriched domains (rafts). This mechanism would be of huge impact for signaling raft proteins, such as e,g., the linker for activation of T-cells (LAT), which putatively first diffuse into a raft domain and then aggregate for signaling. We therefore propose to elucidate the role of membrane curvature strain in the aggregation behavior of de-novo designed transmembrane proteins of specific shape using an array of experimental techniques.