Streptavidin/biotin: Tethering geometry defines unbinding mechanics.

Abstract:

:Macromolecules tend to respond to applied forces in many different ways. Chemistry at high shear forces can be intriguing, with relatively soft bonds becoming very stiff in specific force-loading geometries. Largely used in bionanotechnology, an important case is 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 to more than 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 causes 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.

journal_name

Sci Adv

journal_title

Science advances

authors

Sedlak SM,Schendel LC,Gaub HE,Bernardi RC

doi

10.1126/sciadv.aay5999

subject

Has Abstract

pub_date

2020-03-25 00:00:00

pages

eaay5999

issue

13

issn

2375-2548

pii

aay5999

journal_volume

6

pub_type

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