TCBG Seminar

“Force propagation through ultrastable cellulosome-adhesion complexes”

Klara Malinowska
Center for Nano Science
Munich, Germany

Monday, August 10, 2015
2:00 pm (CT)
4269 Beckman Institute


Challenging environments have guided nature in the development of ultrastable protein complexes. In cellulosomes, where network assembly is enabled by protein interactions with commonplace affinities, we show that certain ligand–receptor interactions exhibit extreme resistance to applied force. Specifically, we characterize the cohesin-dockerin complex responsible for substrate anchoring in the Ruminococcus flavefaciens cellulosome using single-molecule force spectroscopy and steered molecular dynamics simulations. The complex withstands forces of 600–750 pN at moderate loading rates, making it one of the strongest bimolecular interactions reported. We demonstrate force activation and inter- domain stabilization of the complex, show how changing the direction of applied force can result in a diversity of mechanical behaviors and suggest that certain network components serve as mechanical effectors for maintaining network integrity. Moreover, a combination of dynamic network analysis and thermodynamic fluctuation theory allowes us to visualize the paths through the protein complex along which force is communicated. Our results provide insight into the molecular origins of the extreme mechanostability of this complex, and implicate specific force-propagation architectures that will be advantageous in designing mechanostable protein interactions for biotechnological applications.

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