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
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...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
- 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
-
Recent Developments of Steroid Sulfatase Inhibitors as Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Hypothalamic Leptin and Ghrelin Signaling as Targets for Improvement in Metabolic Control
Current Pharmaceutical Design New Perspective Therapy of Breast Cancer Based on Selective Dopamine Receptor D2 Agonist and Antagonist Effects on MCF-7 Cell Line
Recent Patents on Anti-Cancer Drug Discovery Genetic Predisposition in NAFLD and NASH: Impact on Severity of Liver Disease and Response to Treatment
Current Pharmaceutical Design Can Diabetes Heal?- From Observations to Perspectives
Current Diabetes Reviews New Therapeutic Strategies for Coeliac Disease: Tissue Transglutaminase as a Target
Current Medicinal Chemistry Lapatinib as a Chemotherapeutic Drug
Recent Patents on Anti-Cancer Drug Discovery Modulation of Angiogenesis by Inflammatory Markers and the Role of Matrix Metalloproteinases in an Endothelial Cell/Fibroblast Co-culture System
Current Angiogenesis (Discontinued) Cardiovascular Physiology of Androgens and Androgen Testosterone Therapy in Postmenopausal Women
Endocrine, Metabolic & Immune Disorders - Drug Targets Ultra-micronized Palmitoylethanolamide Effects on Sleep-wake Rhythm and Neuropathic Pain Phenotypes in Patients with Carpal Tunnel Syndrome: An Open-label, Randomized Controlled Study
CNS & Neurological Disorders - Drug Targets Advanced Methods for the Analysis of Testosterone
Current Medicinal Chemistry Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors
Current Cancer Drug Targets Epigenetic Effects of Environmental Chemicals on Reproductive Biology
Current Drug Targets Modifications of the Immune Responsiveness in Patients with Autoimmune Thyroiditis: Evidence for a Systemic Immune Alteration
Current Pharmaceutical Design Different Aspects of Head and Neck Squamous Cell Carcinoma: Cancer Stem Cells, their Niche and Targeted Therapy
Current Stem Cell Research & Therapy Advances in Biomarker Research for Pancreatic Cancer
Current Pharmaceutical Design Advances in Osteoclast Differentiation and Function
Current Drug Targets - Immune, Endocrine & Metabolic Disorders New Prognostic Markers and Potential Therapeutic Targets in Human Testicular Germ Cell Tumors
Current Medicinal Chemistry Inflammation, High Density Lipoprotein and Endothelium
Current Medicinal Chemistry Exciting News from the Messenger
Current Neurovascular Research