, Umeå researchers describe a natural product-like molecule, Tantalosin, that inhibits interaction between two proteins in complexes that reshape membranes inside the cell. The findings lead to a deeper understanding of how membrane remodelling works in human cells and future development of new drugs.
Previously, Professor Yaowen Wu and his group, in collaboration with Professor Herbert Waldmann's laboratory at Max Planck Institute Dortmund in Germany, identified a chemical molecule, Tantalosin, that induces a phenotype like autophagy -- a self-eating process in the cell. Tantalosin is a synthetic molecule inspired by alkaloids from the medical plant Cinchona.
The researchers characterized the mechanism using a range of biochemical and cell biological methods. When they studied protein-protein interaction in solution, they found that Tantalosin completely stops the interaction between IST1 and its binding partner CHMP1B. In this study, the researchers found that LC3 protein, which is usually a hallmark of autophagy, is linked to the endosomal membranes during Tantalosin treatment. Interestingly, the canonical autophagic degradation was not observed. Instead, they found that the process follows a noncanonical autophagy pathway.
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