Abstract
The interleukin-10 (IL-10) family of cytokines includes IL-10, a number of its viral gene homologs, and eight recently discovered cellular cytokines (IL-19, IL-20, IL-22, IL-24, IL-26, IFN-l1, IFN-λ2, IFN-λ3). IL-10 is an intercalated dimer consisting of two six-helix bundle domains. Signal transduction occurs when each domain of IL-10 binds to two receptor chains, IL-10R1 and IL-10R2. Viral homologs use the same IL-10 receptor system, while cellular homologs use their own receptors: three long receptor chains (IL-20R1, IL-22R1 and IFN-λ1R1) and two short receptor chains (IL-20R2 and IL-10R2). Most of the cellular homologs belong to the IL-19 subfamily of cytokines including IL-19, IL-20, IL-22 and IL-24. It is likely that IFN-λ1, IFN-λ2, and IFN-λ3 also belong to the same subfamily. All these proteins are monomers in solution. Crystal structures of IL-19 and IL-22 show that the molecules consist of seven helices (A-G) forming a seven-helix bundle with compact hydrophobic core inside. Structures of complexes of IL-10 and CMVIL-10 with an extracellular domain of high affinity receptor IL-10R1 (sIL-10R1) showed that ligand / receptor interactions are of mostly polar nature, with two hydrophobic patches around receptor residues Tyr43 and Phe143 at the top and bottom of the interface. The location and structure of the binding site for the second receptor chain are still unknown. It has also been shown that in the case of IL-19 and IL-20, IL-20R2 rather than IL-20R1 is a high-affinity receptor chain. This review summarizes all published three-dimensional structures of the cytokines representing the IL-10 family of homologs, including the IL-19 subfamily and their interaction with appropriate receptors.
Keywords: cytokines, interleukin-10, ligand/receptor interactions, helix bundle, signal transduction
Current Pharmaceutical Design
Title: Structural Features of the Interleukin-10 Family of Cytokines
Volume: 10 Issue: 31
Author(s): Alexander Zdanov
Affiliation:
Keywords: cytokines, interleukin-10, ligand/receptor interactions, helix bundle, signal transduction
Abstract: The interleukin-10 (IL-10) family of cytokines includes IL-10, a number of its viral gene homologs, and eight recently discovered cellular cytokines (IL-19, IL-20, IL-22, IL-24, IL-26, IFN-l1, IFN-λ2, IFN-λ3). IL-10 is an intercalated dimer consisting of two six-helix bundle domains. Signal transduction occurs when each domain of IL-10 binds to two receptor chains, IL-10R1 and IL-10R2. Viral homologs use the same IL-10 receptor system, while cellular homologs use their own receptors: three long receptor chains (IL-20R1, IL-22R1 and IFN-λ1R1) and two short receptor chains (IL-20R2 and IL-10R2). Most of the cellular homologs belong to the IL-19 subfamily of cytokines including IL-19, IL-20, IL-22 and IL-24. It is likely that IFN-λ1, IFN-λ2, and IFN-λ3 also belong to the same subfamily. All these proteins are monomers in solution. Crystal structures of IL-19 and IL-22 show that the molecules consist of seven helices (A-G) forming a seven-helix bundle with compact hydrophobic core inside. Structures of complexes of IL-10 and CMVIL-10 with an extracellular domain of high affinity receptor IL-10R1 (sIL-10R1) showed that ligand / receptor interactions are of mostly polar nature, with two hydrophobic patches around receptor residues Tyr43 and Phe143 at the top and bottom of the interface. The location and structure of the binding site for the second receptor chain are still unknown. It has also been shown that in the case of IL-19 and IL-20, IL-20R2 rather than IL-20R1 is a high-affinity receptor chain. This review summarizes all published three-dimensional structures of the cytokines representing the IL-10 family of homologs, including the IL-19 subfamily and their interaction with appropriate receptors.
Export Options
About this article
Cite this article as:
Zdanov Alexander, Structural Features of the Interleukin-10 Family of Cytokines, Current Pharmaceutical Design 2004; 10 (31) . https://dx.doi.org/10.2174/1381612043382602
DOI https://dx.doi.org/10.2174/1381612043382602 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Effects of Brain IKKβ Gene Silencing by Small Interfering RNA on P-Glycoprotein Expression and Brain Damage in the Rat Kainic Acid-Induced Seizure Model
CNS & Neurological Disorders - Drug Targets Vasculogenic and Angiogenic Pathways in Moyamoya Disease
Current Medicinal Chemistry Cancer-Homing Toxins
Current Pharmaceutical Design The 18 kDa Mitochondrial Translocator Protein (TSPO) Prevents Accumulation of Protoporphyrin IX. Involvement of Reactive Oxygen Species (ROS)
Current Molecular Medicine Tumour Targeting with Systemically Administered Bacteria
Current Gene Therapy 2D, 3D, G-QSAR and Docking Studies of Thiazolyl-pyrazoline Analogues as Potent (Epidermal Growth Factor Receptor-tyrosine Kinase) EGFR-TK Inhibitors
Letters in Drug Design & Discovery Recent Patents, Formulation and Characterization of Nanoliposomes
Recent Patents on Drug Delivery & Formulation Pathobiology and Therapeutic Implications of Tumor Acidosis
Current Medicinal Chemistry Recent Advances in Optical Molecular Imaging and its Applications in Targeted Drug Delivery
Current Drug Targets Atypical PKCι as Target for Glioblastoma Therapy
Current Cancer Drug Targets Mesenchymal Stem/Stromal Cells: A New "Cells as Drugs" Paradigm. Efficacy and Critical Aspects in Cell Therapy
Current Pharmaceutical Design Nucleic Acids as Therapeutic Agents
Current Topics in Medicinal Chemistry Opportunities and Challenges for Host-Directed Therapies in Tuberculosis
Current Pharmaceutical Design Progress in Drug Treatment of Cerebral Edema
Mini-Reviews in Medicinal Chemistry CD44 and EpCAM: Cancer-Initiating Cell Markers
Current Molecular Medicine Endothelial Cell Heterogeneity: A Developmental Biologist’s Perspective
Current Angiogenesis (Discontinued) Resveratrol Protects β Amyloid-Induced Oxidative Damage and Memory Associated Proteins in H19-7 Hippocampal Neuronal Cells
Current Alzheimer Research Inflammasome as a New Therapeutic Target for Diabetic Complications
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery BRCA-FA Pathway as a Target for Anti-Tumor Drugs
Anti-Cancer Agents in Medicinal Chemistry Immunopathology of Type 1 Diabetes and Immunomodulatory Effects of Stem Cells: A Narrative Review of the Literature
Endocrine, Metabolic & Immune Disorders - Drug Targets