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bioRxiv · 10.1101/593335

Is mechanical receptor ligand dissociation driven by unfolding or unbinding?

Milles, L.·Gaub, H. E.
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Abstract

Mechanical force can play a pivotal role in biological systems. Single Molecule Force Spectroscopy, is a powerful tool to probe the mechanics of proteins and their binding partners. Yet, it remains unclear how complex dissociation of a protein-protein interaction under mechanical forces occurs. Are receptor and ligand unbinding, or are they unfolding? We utilize an approach wherein receptor and ligand are expressed as a single molecule fused by a long flexible linker. Force is applied to the complex via an ultrastable handle. Consequently, the events during and following complex dissociation can be monitored. We investigate two high-affinity systems: The cohesin-dockerin type I interaction in which we find that a binding partner unfolds upon complex dissociation, and a colicin-immunity protein complex in which both proteins unfold completely upon unbinding. Mechanical receptor ligand dissociation thus can encompass unfolding of one or both binding partners.

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Milles, L., Gaub, H. E.. 2019-04-02. Is mechanical receptor ligand dissociation driven by unfolding or unbinding?. https://doi.org/10.1101/593335

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