Abstract
PDZ domains play an essential role in a number of cellular processes by facilitating protein scaffolding and assembly of protein complexes. These domains consist of 80 to 90 amino acids and are found to recognize short C-terminal sequences of target proteins. Protein complex formation between PDZ target molecules can lead to a number of signaling and regulatory cascades that may either promote or inhibit the activation of certain proteins. It has been shown that the interaction of the PDZ domains of NHERF2 with LPA2 plays an inhibitory role on the cystic fibrosis transmembrane conductance regulator (CFTR) by promoting the assembly of a CFTR–NHERF2–LPA2 complex. CFTR regulates chloride ion transport across the epithelial plasma membrane, and individuals possessing CFTR mutations show decreased protein function and consequently, viscous mucus accumulation due to improper fluid transport. This type of ailment is termed cystic fibrosis. Thus, insight to the structure of PDZ domains and how they function to form macromolecular complexes could be therapeutically important in augmenting CFTR channel activity in cystic fibrosis patients. Here we review the PDZ domain family while dissecting their structure, function and implications in CFTR regulation and cystic fibrosis.
Keywords: CFTR, cystic fibrosis, drug design, NHERF1/2, PDZ, structure.
Graphical Abstract
Current Drug Targets
Title:PDZ Structure and Implication in Selective Drug Design against Cystic Fibrosis
Volume: 16 Issue: 9
Author(s): Joshua Holcomb, Nicholas Spellmon, Laura Trescott, Fei Sun, Chunying Li and Zhe Yang
Affiliation:
Keywords: CFTR, cystic fibrosis, drug design, NHERF1/2, PDZ, structure.
Abstract: PDZ domains play an essential role in a number of cellular processes by facilitating protein scaffolding and assembly of protein complexes. These domains consist of 80 to 90 amino acids and are found to recognize short C-terminal sequences of target proteins. Protein complex formation between PDZ target molecules can lead to a number of signaling and regulatory cascades that may either promote or inhibit the activation of certain proteins. It has been shown that the interaction of the PDZ domains of NHERF2 with LPA2 plays an inhibitory role on the cystic fibrosis transmembrane conductance regulator (CFTR) by promoting the assembly of a CFTR–NHERF2–LPA2 complex. CFTR regulates chloride ion transport across the epithelial plasma membrane, and individuals possessing CFTR mutations show decreased protein function and consequently, viscous mucus accumulation due to improper fluid transport. This type of ailment is termed cystic fibrosis. Thus, insight to the structure of PDZ domains and how they function to form macromolecular complexes could be therapeutically important in augmenting CFTR channel activity in cystic fibrosis patients. Here we review the PDZ domain family while dissecting their structure, function and implications in CFTR regulation and cystic fibrosis.
Export Options
About this article
Cite this article as:
Holcomb Joshua, Spellmon Nicholas, Trescott Laura, Sun Fei, Li Chunying and Yang Zhe, PDZ Structure and Implication in Selective Drug Design against Cystic Fibrosis, Current Drug Targets 2015; 16 (9) . https://dx.doi.org/10.2174/1389450116666141219120125
DOI https://dx.doi.org/10.2174/1389450116666141219120125 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Related Books

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Human Tissue Kallikrein: A New Bullet for the Treatment of Ischemia
Current Pharmaceutical Design Genomic Instability and Cancer
Current Molecular Medicine Therapeutical Approaches of Vasoactive Intestinal Peptide as a Pleiotropic Immunomodulator
Current Pharmaceutical Design Regulatory Role of G Protein-coupled Receptors in Pancreatic Cancer Development and Progression
Current Medicinal Chemistry Human UDP-Glucuronosyltransferase 2B7
Current Drug Metabolism Anticancer Drug Discovery Targeting DNA Hypermethylation
Current Medicinal Chemistry EMT Blockage Strategies: Targeting Akt Dependent Mechanisms for Breast Cancer Metastatic Behaviour Modulation
Current Gene Therapy Selectively Replicating Adenoviruses for Oncolytic Therapy
Current Cancer Drug Targets Associating Paracrine Communication to Regenerative Medicine: Search Strategies & Major Trends in Scientific and Patent Production
Recent Patents on Regenerative Medicine Aspects of the Cytotoxic Action of Ribonucleases
Current Pharmaceutical Biotechnology Neurodegeneration in the Pathogenesis of Diabetic Retinopathy: Molecular Mechanisms and Therapeutic Implications
Current Medicinal Chemistry Nanomedicines as Cancer Therapeutics: Current Status
Current Cancer Drug Targets Adipose Tissue-Derived Pericytes for Cartilage Tissue Engineering
Current Stem Cell Research & Therapy p38 MAP Kinase Interacts with and Stabilizes Pancreatic and Duodenal Homeobox-1
Current Molecular Medicine Human Aurora / Ipl1p Related Kinases
Current Genomics Keratin-Based Biomaterials for Biomedical Applications
Current Drug Targets Chronic Inflammatory Diseases and the Acute Respiratory Distress Syndrome (ARDS)
Current Pharmaceutical Design Chemotherapeutic Properties of n-3 Polyunsaturated Fatty Acids - Old Concepts and New Insights
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Molecular Pathways Linking Inflammation and Cancer
Current Molecular Medicine Synthesis, Characterization and In Vitro Evaluation of Self-Assembled poly(ethylene glycol)-glycyrrhetinic Acid Conjugates
Letters in Organic Chemistry