Calcium binding to L-plastin regulates actin bundling: a target for new anti-metastasis drugs? – Biologisk Institut - Københavns Universitet

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Calcium binding to L-plastin regulates actin bundling: a target for new anti-metastasis drugs?

Speaker: Professor Hans Vogel, University of Calgary

Host:
Professor Birthe Kragelund, Section of Molecular Sciences

Abstract
The plastin proteins, also known as fimbrins, are found in all eukaryotic organisms, where they are involved in actin-bundling. They have a unique multidomain structure made up of four CH domains and two EF-hand calcium binding motifs. The four CH domains are directly involved in the  bundling of F-actin, while binding of calcium to the EF-hand headpiece of the protein can inhibit this process. Using NMR spectroscopy and various biophysical methods, we have studied the calcium-binding headpiece domains of L-plastin and various other plastics/fimbrins. Our results reveal an unexpected activation mechanism, involving a flexible region in the apo-protein. L-plastin is normally only expressed in white blood cells, but it also is highly expressed in metastatic cancer cells, making this protein a potential target for the development of new anticancer drugs.