Kathryn Shelley | Cycling protein conformations with light
Foresight Institute Molecular Machines Group
Cycling protein conformations with light
Abstract: A grand challenge in synthetic biology is to build de novo protein nanomachines. However, a component all nanomachines require, not yet designed in a de novo protein, is a motor that converts biochemical energy into the mechanical work needed to coordinate its activity.
The Baker lab recently published a series of de novo “hinge” proteins that irreversibly switch between two defined conformations upon addition of a binding partner. We have designed these hinges into light-driven protein motor domains that can rapidly cycle back and forth between their two conformational states by crosslinking them to the photoswitchable small molecule azobenzene. We can modulate the cycling behaviour of our motor domains by redesigning their shape changes and/or affinities for their binding partners. We have also designed motor domains that interact with bioactive binding partners, such as the pro-apoptotic peptide BIM-BH3 whose binding and release we can cycle to trigger cell death.
Our motor domains are modular components that can be easily fused to other proteins. This has enabled us to utilize our designs for applications ranging from cycling hydrogel stiffness to controlling protein localization on a surface, and will enable their ready incorporation into future nanomachine designs.
Bio: Kathryn is a postdoctoral researcher tackling the challenge of incorporating movement into de novo protein designs. She completed her PhD in protein design in Dek Woolfson’s lab at the University of Bristol, where she contributed to the design of a differential biosensor to measure unique “fingerprints” of complex mixtures – such as blood samples – and identify common features between samples from different patient groups. During her PhD Kathryn also got her first taste of designing conformationally dynamic proteins, which inspired her to pursue this research area further during her postdoctoral research. She is currently a postdoc in David Baker’s lab at the University of Washington, where she is designing de novo proteins that undergo conformational change in response to different environmental stimuli. https://www.linkedin.com/in/kathryn-shelley-b494b9150
Foresight Institute Molecular Machines Group
A group of scientists, entrepreneurs, and institutional allies who cooperate to advance molecular machines, applications in energy, medicine, and material science, and long-term progress toward Richard Feynman’s vision of nanotechnology.
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