Protein Allostery at Atomic Resolution
- Author(s)
- D. Strotz, J. Orts, H. Kadavath, M. Friedmann, D. Ghosh, S. Olsson, C. N. Chi, A. Pokharna, P. Guntert, B. Vogeli, R. Riek
- Abstract
Protein allostery is a phenomenon involving the long range coupling between two distal sites in a protein. In order to elucidate allostery at atomic resoluion on the ligand-binding WW domain of the enzyme Pin1, multistate structures were calculated from exact nuclear Overhauser effect (eNOE). In its free form, the protein undergoes a microsecond exchange between two states, one of which is predisposed to interact with its parent catalytic domain. In presence of the positive allosteric ligand, the equilibrium between the two states is shifted towards domain–domain interaction, suggesting a population shift model. In contrast, the allostery-suppressing ligand decouples the side-chain arrangement at the inter-domain interface thereby reducing the inter-domain interaction. As such, this mechanism is an example of dynamic allostery. The presented distinct modes of action highlight the power of the interplay between dynamics and function in the biological activity of proteins.
- Organisation(s)
- External organisation(s)
- Eidgenössische Technische Hochschule Zürich, Freie Universität Berlin (FU), Uppsala University, Johann Wolfgang Goethe-Universität Frankfurt am Main, Tokyo Metropolitan University, University of Colorado, Denver
- Journal
- Angewandte Chemie (International Edition)
- Volume
- 59
- Pages
- 22132-22139
- No. of pages
- 8
- ISSN
- 1433-7851
- DOI
- https://doi.org/10.1002/anie.202008734
- Publication date
- 12-2020
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106006 Biophysics, 106002 Biochemistry
- Keywords
- ASJC Scopus subject areas
- Chemistry(all), Catalysis
- Portal url
- https://ucris.univie.ac.at/portal/en/publications/protein-allostery-at-atomic-resolution(b02ac183-04df-4fcf-b1d6-d5bf570694f0).html