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 SA’s 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 SA’s binding pocket lowering the energy barrier, which biotin has to
overcome to escape the pocket.
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