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Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin.

Publication ,  Journal Article
Settanni, G; Serquera, D; Marszalek, PE; Paci, E; Itzhaki, LS
Published in: PLoS computational biology
January 2013

Ankyrin repeat proteins are elastic materials that unfold and refold sequentially, repeat by repeat, under force. Herein we use atomistic molecular dynamics to compare the mechanical properties of the 7-ankyrin-repeat oncoprotein 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, and the mechanical 'hot spots' of the interaction map to the same repeats as the thermodynamic hot spots. A consequence of stepwise nature of unfolding and 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 accessed, 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.

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Published In

PLoS computational biology

DOI

EISSN

1553-7358

ISSN

1553-734X

Publication Date

January 2013

Volume

9

Issue

1

Start / End Page

e1002864

Related Subject Headings

  • Stress, Mechanical
  • Proto-Oncogene Proteins
  • Protein Binding
  • Proteasome Endopeptidase Complex
  • Molecular Dynamics Simulation
  • Models, Molecular
  • Ligands
  • Bioinformatics
  • 08 Information and Computing Sciences
  • 06 Biological Sciences
 

Citation

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Settanni, G., Serquera, D., Marszalek, P. E., Paci, E., & Itzhaki, L. S. (2013). Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin. PLoS Computational Biology, 9(1), e1002864. https://doi.org/10.1371/journal.pcbi.1002864
Settanni, Giovanni, David Serquera, Piotr E. Marszalek, Emanuele Paci, and Laura S. Itzhaki. “Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin.PLoS Computational Biology 9, no. 1 (January 2013): e1002864. https://doi.org/10.1371/journal.pcbi.1002864.
Settanni G, Serquera D, Marszalek PE, Paci E, Itzhaki LS. Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin. PLoS computational biology. 2013 Jan;9(1):e1002864.
Settanni, Giovanni, et al. “Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin.PLoS Computational Biology, vol. 9, no. 1, Jan. 2013, p. e1002864. Epmc, doi:10.1371/journal.pcbi.1002864.
Settanni G, Serquera D, Marszalek PE, Paci E, Itzhaki LS. Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin. PLoS computational biology. 2013 Jan;9(1):e1002864.

Published In

PLoS computational biology

DOI

EISSN

1553-7358

ISSN

1553-734X

Publication Date

January 2013

Volume

9

Issue

1

Start / End Page

e1002864

Related Subject Headings

  • Stress, Mechanical
  • Proto-Oncogene Proteins
  • Protein Binding
  • Proteasome Endopeptidase Complex
  • Molecular Dynamics Simulation
  • Models, Molecular
  • Ligands
  • Bioinformatics
  • 08 Information and Computing Sciences
  • 06 Biological Sciences