SKM 2023 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 23: Single Molecule Biophysics
BP 23.1: Hauptvortrag
Donnerstag, 30. März 2023, 09:30–10:00, BAR 0106
Conformational dynamics of SARS-CoV-2 spike protein modulates the binding affinity to ACE2 — Fidan Sumbul1, Claire Valotteau1, Prithwidip Saha1, Ignacio Fernadez2, Annalisa Meola2, Eduard Baquero2, Dorota Kostrz3, James R Portman3, François Stransky3, Pablo Guardado Calvo2, Charlie Gosse3, Terence Strick3, Felix Rey2, and •Felix Rico1 — 1Aix-Marseille Univ, CNRS, INSERM, LAI, CENTURI, Marseille, France — 2Institut Pasteur, Department of Virology, CNRS UMR 3569, Paris France — 3Ecole Normale Superieure, Institut de Biologie, CNRS, INSERM, PSL, Paris, France
SARS-CoV-2 spike protein (S) interacts with angiotensin-converting enzyme 2 (ACE2) to enter host cells. Protein S forms a homotrimer with three receptor-binding domains (RBD) adopting open and closed conformations. The (un)binding of S to ACE2 may be affected by these conformational dynamics. Here, we used single molecule force spectroscopy to probe the binding strength and affinity of the S-trimer/ACE2 interaction and high-speed atomic force microscopy (HS-AFM) to visualize the RBD opening dynamics of S-trimers. HS-AFM imaging revealed dynamic S-trimers with the three RBDs stochastically and independently switching between open and closed conformations. This modulates binding to ACE2 of S-trimers, but not unbinding. Experimental opening rates and a simple conformational binding model explain the modulation of the binding affinity. Our results shed light on the molecular basis of coronavirus infection.