Effects of Ligand Binding on the Mechanical Properties of Ankyrin Repeat Protein Gankyrin
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Giovanni Settanni
- David Serquera
- Piotr E Marszalek
- Emanuele Paci
- Laura S Itzhaki
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000314595600022&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1371/journal.pcbi.1002864
- eISSN
- 1553-7358
- Externe Identifier
- Clarivate Analytics Document Solution ID: 085ED
- PubMed Identifier: 23341763
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- PLOS COMPUTATIONAL BIOLOGY
- Artikelnummer
- ARTN e1002864
- Datum der Veröffentlichung
- 2013
- Status
- Published
- Titel
- Effects of Ligand Binding on the Mechanical Properties of Ankyrin Repeat Protein Gankyrin
- Sub types
- Article
- Ausgabe der Zeitschrift
- 9
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Giovanni Settanni
- David Serquera
- Piotr E Marszalek
- Emanuele Paci
- Laura S Itzhaki
- DOI
- 10.1371/journal.pcbi.1002864
- Editoren
- Shi-Jie Chen
- eISSN
- 1553-7358
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- PLoS Computational Biology
- Sprache
- en
- Online publication date
- 2013
- Paginierung
- e1002864 - e1002864
- Status
- Published online
- Herausgeber
- Public Library of Science (PLoS)
- Herausgeber URL
- http://dx.doi.org/10.1371/journal.pcbi.1002864
- Datum der Datenerfassung
- 2018
- Titel
- Effects of Ligand Binding on the Mechanical Properties of Ankyrin Repeat Protein Gankyrin
- Ausgabe der Zeitschrift
- 9
Datenquelle: Crossref
- Abstract
- 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.
- Addresses
- Physics Department, Johannes Gutenberg University, Mainz, Germany. settani@uni-mainz.de
- Autoren
- Giovanni Settanni
- David Serquera
- Piotr E Marszalek
- Emanuele Paci
- Laura S Itzhaki
- DOI
- 10.1371/journal.pcbi.1002864
- eISSN
- 1553-7358
- Externe Identifier
- PubMed Identifier: 23341763
- PubMed Central ID: PMC3547791
- Funding acknowledgements
- MRF: MRF_C0385
- Medical Research Foundation: C0385
- NIGMS NIH HHS: R01-GM079563
- Medical Research Council: G1002329
- NIGMS NIH HHS: R01 GM079563
- Open access
- true
- ISSN
- 1553-734X
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- PLoS computational biology
- Schlüsselwörter
- Proteasome Endopeptidase Complex
- Proto-Oncogene Proteins
- Ligands
- Protein Binding
- Stress, Mechanical
- Models, Molecular
- Molecular Dynamics Simulation
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2013
- Open access status
- Open Access
- Paginierung
- e1002864
- Datum der Veröffentlichung
- 2013
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2013
- Titel
- Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Research Support, N.I.H., Extramural
- Ausgabe der Zeitschrift
- 9
Files
https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002864&type=printable https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23341763/pdf/?tool=EBI https://europepmc.org/articles/PMC3547791?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- 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.
- Date of acceptance
- 2012
- Autoren
- Giovanni Settanni
- David Serquera
- Piotr E Marszalek
- Emanuele Paci
- Laura S Itzhaki
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/23341763
- DOI
- 10.1371/journal.pcbi.1002864
- eISSN
- 1553-7358
- Externe Identifier
- PubMed Central ID: PMC3547791
- Funding acknowledgements
- MRF: MRF_C0385
- NIGMS NIH HHS: R01 GM079563
- Medical Research Council: G1002329
- NIGMS NIH HHS: R01-GM079563
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- PLoS Comput Biol
- Schlüsselwörter
- Ligands
- Models, Molecular
- Molecular Dynamics Simulation
- Proteasome Endopeptidase Complex
- Protein Binding
- Proto-Oncogene Proteins
- Stress, Mechanical
- Sprache
- eng
- Country
- United States
- Paginierung
- e1002864
- PII
- PCOMPBIOL-D-12-01119
- Datum der Veröffentlichung
- 2013
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2013
- Titel
- Effects of ligand binding on the mechanical properties of ankyrin repeat protein gankyrin.
- Sub types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 9
Datenquelle: PubMed
- Beziehungen:
- Eigentum von