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Laura Galazzo (left) and Enrica Bordignon use tiny parts of antibodies to examine proteins in detail. © RUB, Marquard
Membrane proteins (grey-blue colors) are embedded in the cell membrane (pink). Nanobodies (yellow and orange), have gadolinium attached to them (red) and bind to the membrane proteins. When the proteins take on a certain shape, these markers are so close that their distance can be detected by EPR spectroscopy. © M.H. Timachi

Observing proteins in their natural environment

PNAS: Proteins can expel active pharmaceutical ingredients from the target cells. Now we can watch them as they do it.

Certain medications, such as those used to treat cancer, lose their effect because proteins in the membrane of the target cell simply expel them again. A team at Ruhr-Universität Bochum (RUB) was able to observe a responsible transport protein in its natural environment for the first time. They labelled it with small sequences of antibodies to which a contrast agent was linked. By detecting the spin of the metal contrast agent with electron paramagnetic resonance spectroscopy (EPR, in short), they could draw conclusions on the state of the protein. The team led by Professor Enrica Bordignon and Dr. Laura Galazzo from the cluster of excellence Ruhr Explores Solvation Resolv in collaboration with Professor Markus Seeger's group from the University of Zurich reports on the method in the journal PNAS on 4 February 2020.

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Detailed Press Release

Original Publication: Laura Galazzo, Gianmarco Meier, M. Hadi Timachi, Cedric A. J. Hutter, Markus A. Seeger, Enrica Bordignon: Spin-labeled nanobodies as protein conformational reporters for electron paramagnetic resonance in cellular membranes, in: PNAS, 2020, DOI: 10.1073/pnas.1913737117

 

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Proteine in ihrer natürlichen Umgebung beobachten

PNAS: Proteine können dafür verantwortilch sein, dass Wirkstoffe von Medikamenten aus den Zielzellen einfach wieder herausgeschleust werden. Dabei kann man ihnen jetzt zuschauen.

Bestimme Medikamente, zum Beispiel gegen Krebserkrankungen, verlieren ihre Wirkung, weil Proteine in der Membran der Zielzelle sie einfach wieder ausschleusen. Ein verantwortliches Transportprotein konnte ein Team der Ruhr-Universität Bochum (RUB) erstmals in seiner natürlichen Umgebung beobachten. Dazu markierten die Forscherinnen und Forscher es mit kleinen Sequenzen von Antikörpern, an denen ein Kontrastmittel angedockt war. Dessen Spin konnten sie mittels Elektronenspinresonanz detektieren und Rückschlüsse auf den Zustand des Proteins ziehen. Über die Methode berichtet das Team um Prof. Dr. Enrica Bordignon und Dr. Laura Galazzo vom Exzellenzcluster Ruhr Explores Solvation Resolv in Zusammenarbeit mit der Gruppe von Prof. Dr. Markus Seeger von der Universität Zürich in der Zeitschrift PNAS vom 4. Februar 2020.

Zusätzliche Information

Ausführliche Presseninformation

Originalveröffentlichung: Laura Galazzo, Gianmarco Meier, M. Hadi Timachi, Cedric A. J. Hutter, Markus A. Seeger, Enrica Bordignon: Spin-labeled nanobodies as protein conformational reporters for electron paramagnetic resonance in cellular membranes, in: PNAS, 2020, DOI: 10.1073/pnas.1913737117

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