Regensburg 2013 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 2: Proteins

BP 2.8: Vortrag

Montag, 11. März 2013, 11:45–12:00, H44

Effects of ligand binding on the mechanical properties of ankyrin repeat proteins — •Giovanni Settanni¹, David Serquera², Piotr Marszalek³, Emanuele Paci⁴, and Laura Itzhaki⁵ — ¹Physics Department, Johannes Gutenberg University, Mainz, Germany — ²Hutchison/MRC Research Centre, Cambridge, UK — ³Duke University, Durham, NC, USA — ⁴University of Leeds, UK — ⁵University of Cambridge, UK

Ankyrin repeat proteins are elastic materials that unfold and refold repeat by repeat, under force. Herein we use atomistic molecular dynamics to compare the mechanical properties of the 7-repeat protein Gankyrin in isolation and in complex with its binding partner S6-C. We show that the bound S6-C greatly increases the resistance of Gankyrin to mechanical stress. The effect is specific to those repeats of Gankyrin directly in contact with S6-C. A consequence of the localized nature of ligand binding is that it impacts on all aspects of the protein's mechanical behavior, including the order of repeat unfolding, the diversity of unfolding pathways, the nature of partially unfolded intermediates, the forces required and the work transferred to the system to unfold the whole protein and its parts. Stepwise unfolding thus provides the means to buffer repeat proteins and their binding partners from mechanical stress in the cell. Our results illustrate how ligand binding can control the mechanical response of proteins. The data also point to a cellular mechano-switching mechanism whereby binding between two partner macromolecules is regulated by mechanical stress.