PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Cryo-EM Evidence Elucidated with AlphaFold2 Computational Prediction Provides Structural Insights into the Complex Modular Structure of GABAA Receptors
Version 1
: Received: 2 July 2024 / Approved: 3 July 2024 / Online: 3 July 2024 (11:37:30 CEST)
How to cite:
Xue, H.; Kan, C.; Ullah, A. Cryo-EM Evidence Elucidated with AlphaFold2 Computational Prediction Provides Structural Insights into the Complex Modular Structure of GABAA Receptors. Preprints2024, 2024070335. https://doi.org/10.20944/preprints202407.0335.v1
Xue, H.; Kan, C.; Ullah, A. Cryo-EM Evidence Elucidated with AlphaFold2 Computational Prediction Provides Structural Insights into the Complex Modular Structure of GABAA Receptors. Preprints 2024, 2024070335. https://doi.org/10.20944/preprints202407.0335.v1
Xue, H.; Kan, C.; Ullah, A. Cryo-EM Evidence Elucidated with AlphaFold2 Computational Prediction Provides Structural Insights into the Complex Modular Structure of GABAA Receptors. Preprints2024, 2024070335. https://doi.org/10.20944/preprints202407.0335.v1
APA Style
Xue, H., Kan, C., & Ullah, A. (2024). Cryo-EM Evidence Elucidated with AlphaFold2 Computational Prediction Provides Structural Insights into the Complex Modular Structure of GABAA Receptors. Preprints. https://doi.org/10.20944/preprints202407.0335.v1
Chicago/Turabian Style
Xue, H., Chloe Kan and Ata Ullah. 2024 "Cryo-EM Evidence Elucidated with AlphaFold2 Computational Prediction Provides Structural Insights into the Complex Modular Structure of GABAA Receptors" Preprints. https://doi.org/10.20944/preprints202407.0335.v1
Abstract
GABAA receptors are channel proteins crucial to mediating neuronal balance in the CNS. The structure of GABAA receptors allows for multiple binding sites and is key to drug development. Yet, the formation mechanism of the receptor’s distinctive pentameric structure is still unknown. This study aims to investigate the role of three predominant subunits of the human GABAA receptor in the formation of protein pentamers. Through purifying and refolding the protein fragments of the GABAA receptor α1, β2, and γ2 subunits, homopentamers were visualised with negative staining and Cryo-EM. To aid the analysis, AlphaFold2 was used to compare the structures. Results show that α1 and β2 subunit fragments successfully formed homo-oligomers, particularly homopentameric structures, while the predominant heteropentameric GABAA receptor was also replicated through the combination of the three subunits. However, it is still unclear whether γ2 subunits can form homopentamers or their main purpose is to bring together the α1 and β2 subunits to form GABAA receptors. Nevertheless, this study will lead to a deeper understanding of the atomic structure of GABAA receptors, especially in the formation mechanism of complex protein structures, and hopefully pave the way to the development of novel therapeutics for neuropsychiatric diseases.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
