Interaction networks within disease-associated Gα S variants characterized by an integrative biophysical approach.
Autor: | Anazia K; Department of Chemistry, University of Florida, Gainesville, Florida, USA., Koenekoop L; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden., Ferré G; Department of Chemistry, University of Florida, Gainesville, Florida, USA., Petracco E; Department of Chemistry, University of Florida, Gainesville, Florida, USA; URD Agro-Biotechnologies Industrielles (ABI), CEBB, AgroParisTech, Pomacle, France., Gutiérrez-de-Terán H; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden. Electronic address: hugo.gutierrez@icm.uu.se., Eddy MT; Department of Chemistry, University of Florida, Gainesville, Florida, USA. Electronic address: matthew.eddy@ufl.edu. |
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Jazyk: | angličtina |
Zdroj: | The Journal of biological chemistry [J Biol Chem] 2024 Aug; Vol. 300 (8), pp. 107497. Date of Electronic Publication: 2024 Jun 24. |
DOI: | 10.1016/j.jbc.2024.107497 |
Abstrakt: | Activation of G proteins through nucleotide exchange initiates intracellular signaling cascades essential for life processes. Under normal conditions, nucleotide exchange is regulated by the formation of G protein-G protein-coupled receptor complexes. Single point mutations in the Gα subunit of G proteins bypass this interaction, leading to loss of function or constitutive gain of function, which is closely linked with the onset of multiple diseases. Despite the recognized significance of Gα mutations in disease pathology, structural information for most variants is lacking, potentially due to inherent protein dynamics that pose challenges for crystallography. To address this, we leveraged an integrative spectroscopic and computational approach to structurally characterize seven of the most frequently observed and clinically relevant mutations in the stimulatory Gα subunit, Gα Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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