Abstract
Heterotrimeric G-proteins, comprising Gα, Gβ, and Gγ subunits, are molecular switches that regulate numerous signaling pathways involved in cellular physiology. This characteristic is achieved by the adoption of two principal states: an inactive state in which GDP-bound Gα is complexed with the Gβγ dimer, and an active state in which GTP-bound Gα is freed of its Gβγ binding partner. Structural studies have illustrated the basis for the distinct conformations of these states which are regulated by alterations in three precise ‘switch regions’ of the Gα subunit. Discrete differences in conformation between GDP- and GTP-bound Gα underlie its nucleotide-dependent protein-protein interactions (e.g., with Gβγ/receptor and effectors, respectively) that are critical for maintaining their proper nucleotide cycling and signaling properties. Recently, several screening approaches have been used to identify peptide sequences capable of interacting with Gα (and free Gβγ) in nucleotide-dependent fashions. These peptides have demonstrated applications in direct modulation of the nucleotide cycle, assessing the structural basis for aspects of Gα and Gβγ signaling, and serving as biosensor tools in assays for Gα activation including high throughput drug screening. In this review, we highlight some of the methods used for such discoveries and discuss the insights that can be gleaned from application of these identified peptides.
Combinatorial Chemistry & High Throughput Screening
Title: State-Selective Binding Peptides for Heterotrimeric G-Protein Subunits:Novel Tools for Investigating G-Protein Signaling Dynamics
Volume: 11 Issue: 5
Author(s): Christopher A. Johnston, Francis S. Willard, J. Kevin Ramer, Rainer Blaesius, C. Natalia Roques and David P. Siderovski
Affiliation:
Abstract: Heterotrimeric G-proteins, comprising Gα, Gβ, and Gγ subunits, are molecular switches that regulate numerous signaling pathways involved in cellular physiology. This characteristic is achieved by the adoption of two principal states: an inactive state in which GDP-bound Gα is complexed with the Gβγ dimer, and an active state in which GTP-bound Gα is freed of its Gβγ binding partner. Structural studies have illustrated the basis for the distinct conformations of these states which are regulated by alterations in three precise ‘switch regions’ of the Gα subunit. Discrete differences in conformation between GDP- and GTP-bound Gα underlie its nucleotide-dependent protein-protein interactions (e.g., with Gβγ/receptor and effectors, respectively) that are critical for maintaining their proper nucleotide cycling and signaling properties. Recently, several screening approaches have been used to identify peptide sequences capable of interacting with Gα (and free Gβγ) in nucleotide-dependent fashions. These peptides have demonstrated applications in direct modulation of the nucleotide cycle, assessing the structural basis for aspects of Gα and Gβγ signaling, and serving as biosensor tools in assays for Gα activation including high throughput drug screening. In this review, we highlight some of the methods used for such discoveries and discuss the insights that can be gleaned from application of these identified peptides.
Export Options
About this article
Cite this article as:
Johnston A. Christopher, Willard S. Francis, Ramer Kevin J., Blaesius Rainer, Roques Natalia C. and Siderovski P. David, State-Selective Binding Peptides for Heterotrimeric G-Protein Subunits:Novel Tools for Investigating G-Protein Signaling Dynamics, Combinatorial Chemistry & High Throughput Screening 2008; 11 (5) . https://dx.doi.org/10.2174/138620708784534798
DOI https://dx.doi.org/10.2174/138620708784534798 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
Integrating Network Pharmacology and Traditional Medicine: A New Perspective in Drug Mechanism Research
Network pharmacology is a network construction and network topology analysis strategy that combines pharmacology and pharmacodynamics. In recent years, network pharmacology has emerged as a powerful tool that can be integrated with pharmacology. Natural products commonly function in multicomponent, multitarget, and multipathway systems. Some examples encompass Ayurveda, traditional Chinese medicines ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
A High Throughput Scintillation Proximity Imaging Assay for Protein Methyltransferases
Combinatorial Chemistry & High Throughput Screening Identification of Novel Breast Cancer Genes based on Gene Expression Profiles and PPI Data
Current Proteomics Chemistry and Health Effects of Bioactive Compounds in Selected Culinary Aromatic Herbs
Current Nutrition & Food Science Antioxidants in the Treatment of Diabetes
Current Diabetes Reviews Interlinking of Hypoxia and Estrogen in Thyroid Cancer Progression
Current Medicinal Chemistry Advancements in Non-steroidal Antiandrogens as Potential Therapeutic Agents for the Treatment of Prostate Cancer
Mini-Reviews in Medicinal Chemistry Fluorinated Molecules as Drugs and Imaging Agents in the CNS
Current Topics in Medicinal Chemistry Lithium - Pharmacological and Toxicological Aspects: The Current State of the Art
Current Medicinal Chemistry Adrenoceptors: Non Conventional Target for Breast Cancer?
Current Medicinal Chemistry Innate Immunity in the Mucosal Immune System
Current Pharmaceutical Design Amino Acid Transporter ATB0,+ as a Delivery System for Drugs and Prodrugs
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Advances in the Treatment of Neurodegenerative Disorders Employing Nanoparticles
Recent Patents on Drug Delivery & Formulation Therapeutic Angiogenesis for Islet Revascularization
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Prevalence and Predictors of Overweight and Obesity in Patients with Pituitary Dysfunctions
Endocrine, Metabolic & Immune Disorders - Drug Targets Proteostasis, an Emerging Therapeutic Paradigm for Managing Inflammatory Airway Stress Disease
Current Molecular Medicine Lessons Learned from Two Decades of Clinical Trial Experience in Gene Therapy for Fanconi Anemia
Current Gene Therapy Advanced Protein Drugs and Formulations
Current Protein & Peptide Science High Throughput Screening for Drug Discovery of Autophagy Modulators
Combinatorial Chemistry & High Throughput Screening Pivotal Role of the Interaction Between Herbal Medicines and Gut Microbiota on Disease Treatment
Current Drug Targets The Roles of Sox Family Genes in Sarcoma
Current Drug Targets