101. Isolation and conformational analysis of the Gα α-helical domain.
- Author
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Ham D, Ahn D, Chung C, and Chung KY
- Subjects
- Models, Molecular, Receptors, G-Protein-Coupled metabolism, Nucleotides metabolism, Signal Transduction, Heterotrimeric GTP-Binding Proteins chemistry
- Abstract
Heterotrimeric G proteins (G proteins), composed of Gα, Gβ, and Gγ subunits, are the major downstream signaling molecules of the G protein-coupled receptors. Upon activation, Gα undergoes conformational changes both in the Ras-like domain (RD) and the α-helical domain (AHD), leading to the dissociation of Gα from Gβγ and subsequent regulation of downstream effector proteins. Gα RD mediate the most of classical functions of Gα. However, the role of Gα AHD is relatively not well elucidated despite its much higher sequence differences between Gα subtypes than those between Gα RD. Here, we isolated AHD from Gαs, Gαi1, and Gαq to provide tools for examining Gα AHD. We investigated the conformational dynamics of the isolated Gα AHD compared to those of the GDP-bound Gα. The results showed higher local conformational dynamics of Gα AHD not only at the domain interfaces but also in regions further away from the domain interfaces. This finding is consistent with the conformation of Gα AHD in the receptor-bound nucleotide-free state. Therefore, the isolated Gα AHD could provide a platform for studying the functions of Gα AHD, such as identification of the Gα AHD-binding proteins., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ka Young Chung reports financial support was provided by Korea Ministry of Science and ICT., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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