Bayesian network models identify co-operative GPCR:G protein interactions that contribute to G protein coupling.
العنوان: | Bayesian network models identify co-operative GPCR:G protein interactions that contribute to G protein coupling. |
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المؤلفون: | Mukhaleva E; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010.; Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010., Ma N; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010., van der Velden WJC; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010., Gogoshin G; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010., Branciamore S; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010.; Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010., Bhattacharya S; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010., Rodin AS; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010.; Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010., Vaidehi N; Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010.; Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010. |
المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Oct 12. Date of Electronic Publication: 2023 Oct 12. |
نوع المنشور: | Preprint |
اللغة: | English |
بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
مستخلص: | Cooperative interactions in protein-protein interfaces demonstrate the interdependency or the linked network-like behavior of interface interactions and their effect on the coupling of proteins. Cooperative interactions also could cause ripple or allosteric effects at a distance in protein-protein interfaces. Although they are critically important in protein-protein interfaces it is challenging to determine which amino acid pair interactions are cooperative. In this work we have used Bayesian network modeling, an interpretable machine learning method, combined with molecular dynamics trajectories to identify the residue pairs that show high cooperativity and their allosteric effect in the interface of G protein-coupled receptor (GPCR) complexes with G proteins. Our results reveal a strong co-dependency in the formation of interface GPCR:G protein contacts. This observation indicates that cooperativity of GPCR:G protein interactions is necessary for the coupling and selectivity of G proteins and is thus critical for receptor function. We have identified subnetworks containing polar and hydrophobic interactions that are common among multiple GPCRs coupling to different G protein subtypes (Gs, Gi and Gq). These common subnetworks along with G protein-specific subnetworks together confer selectivity to the G protein coupling. This work underscores the potential of data-driven Bayesian network modeling in elucidating the intricate dependencies and selectivity determinants in GPCR:G protein complexes, offering valuable insights into the dynamic nature of these essential cellular signaling components. Competing Interests: Declaration Of Interests The authors declare no competing interests. |
التعليقات: | Update in: J Biol Chem. 2024 Jun;300(6):107362. doi: 10.1016/j.jbc.2024.107362. (PMID: 38735478) |
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معلومات مُعتمدة: | R01 GM117923 United States GM NIGMS NIH HHS; R01 LM013138 United States LM NLM NIH HHS; R01 LM013876 United States LM NLM NIH HHS |
فهرسة مساهمة: | Keywords: Bayesian network; G protein selectivity; GPCRs; Molecular Dynamics |
تواريخ الأحداث: | Date Created: 20231024 Latest Revision: 20240702 |
رمز التحديث: | 20240702 |
مُعرف محوري في PubMed: | PMC10592737 |
DOI: | 10.1101/2023.10.09.561618 |
PMID: | 37873104 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2692-8205 |
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DOI: | 10.1101/2023.10.09.561618 |