idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
• Defective cellular adhesion plays a central role in cancer and immune reactions
• Talin is one of the key proteins involved in the machinery of cellular adhesion
• The entire structure of talin has been determined with the help of cryo-electron microscopy
• Now the protein’s regulation mechanism can be explained
All complex organisms are made up of cells that are in contact with each other or with structures in intercellular spaces. Cells have contact points on their surface that enable them to maintain physical contact with their environment. However, these connections are dynamic, not static. A finely regulated process of cellular attachments and detachments is particularly important during cell migration, cell development, immune responses and blood clotting. For this reason, the contact points form an elaborate protein machinery.
Talin and integrin, two key proteins in the cellular adhesion machinery, have been the subject of much research in recent years. Together with her team, Naoko Mizuno, head of the “Cellular and Membrane Trafficking” Research Group at the Max Planck Institute of Biochemistry, has now elucidated the structure and regulatory mechanism of talin with the help of cryo-electron microscopy. “Although talin is recognized as key for the cell migration, its regulation was enigmatic as the architecture of the molecule as a whole was unknown,” Mizuno says.
Dirk Dedden, lead author of the study, comments: “We’ve focused on analyzing the protein as a whole. Using a variety of modern biophysical techniques, we’ve discovered which environmental conditions cause the protein to alter its state reversibly.” Thanks to controllable laboratory conditions, the scientists have now been able to determine the protein’s precise molecular structure by means of cryo-electron microscopy.
Talin, like a mechanical spring, is spherical in shape in its inactive form and oblong in its active state. The researchers have now been able to identify which areas of inactive talin are shielded from the environment in its spherical self-inhibitory state. This means that neighbouring proteins are unable to interact with the molecule, and the cell itself is unable to adhere to surrounding tissue. In its elongated active form, the molecule acts as a binding platform for neighbouring proteins, which furthermore promotes attachment of the cell to its surrounding structures.
Naoko Mizuno explains: “Given that the cellular adhesion process no longer functions properly in some diseases, notably cancer, our results will hopefully have long-term medical benefits. Talin is known to activate integrin, and integrin is a well-known target for some anticancer drugs. We hope that an understanding of the regulatory process of the adhesion mechanism will shed light on disease processes and lead to new treatments.”
Naoko Mizuno, PhD
Cellular and Membrane Trafficking
Max Planck Institute of Biochemistry
Am Klopferspitz 18
82152 Martinsried
Germany
E-Mail: mizuno@biochem.mpg.de
http://www.biochem.mpg.de/en/rg/mizuno
D. Dedden, S. Schumacher, C. F. Kelley, M. Zacharias, C. Biertümpfel, R. Fässler, N. Mizuno: The architecture of talin1 reveals an autoinhibition 1 mechanism. Cell, September 2019
https://doi.org/10.1016/j.cell.2019.08.034
Regulatory mechanism of talin: from the spherical, inhibited state to the elongated and active form
Picture: ©Naoko Mizuno, MPI of Biochemistry
None
Merkmale dieser Pressemitteilung:
Journalisten, Lehrer/Schüler, Studierende, Wissenschaftler
Biologie, Chemie, Medizin
überregional
Forschungsergebnisse, Wissenschaftliche Publikationen
Englisch
Regulatory mechanism of talin: from the spherical, inhibited state to the elongated and active form
Picture: ©Naoko Mizuno, MPI of Biochemistry
None
Sie können Suchbegriffe mit und, oder und / oder nicht verknüpfen, z. B. Philo nicht logie.
Verknüpfungen können Sie mit Klammern voneinander trennen, z. B. (Philo nicht logie) oder (Psycho und logie).
Zusammenhängende Worte werden als Wortgruppe gesucht, wenn Sie sie in Anführungsstriche setzen, z. B. „Bundesrepublik Deutschland“.
Die Erweiterte Suche können Sie auch nutzen, ohne Suchbegriffe einzugeben. Sie orientiert sich dann an den Kriterien, die Sie ausgewählt haben (z. B. nach dem Land oder dem Sachgebiet).
Haben Sie in einer Kategorie kein Kriterium ausgewählt, wird die gesamte Kategorie durchsucht (z.B. alle Sachgebiete oder alle Länder).
