TCB Publications - Abstract

Steffen M. Sedlak, Leonard C. Schendel, Hermann E. Gaub, and Rafael C. Bernardi. Streptavidin/biotin: Tethering geometry defines unbinding mechanics. Science Advances, 6:eaay5999, 2020.

SEDL2020-RB Macromolecules tend to respond to applied forces in many different ways. Indeed, chemistry at high shear forces can be intriguing, with relatively soft bonds becoming very stiff in specific force-loading geometries. Largely employed in bionanotechnology, an important case is the one of the streptavidin (SA)/biotin interaction. Although SAs four subunits have the same affinity, we find that the forces required to break the SA/biotin bond depend strongly on the attachment geometry. With AFM-based single-molecule force spectroscopy (SMFS), we measured unbinding forces of biotin from different SA subunits to range from 100 pN to over 400 pN. Using a wide-sampling approach, we carried out hundreds of all-atom steered molecular dynamics (SMD) simulations for the entire system, including molecular linkers. Our strategy revealed the molecular mechanism that leads to a fourfold difference in mechanical stability: Certain force-loading geometries induce conformational changes in SAs binding pocket lowering the energy barrier, which biotin has to overcome to escape the pocket.

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