Abstract
The receptor-type protein-tyrosine phosphatase (RPTP) phogrin is localized at the membrane of secretory granules of pancreatic islet β-cells and, similarly to the closely related ICA512, plays a role in the regulation of insulin secretion, in ensuring proper granulogenesis and stability, and in the regulation of β-cell growth. The mature membraneproximal ectodomain of phogrin (MPE phogrin) was produced as a recombinant protein and characterized. CD, fluorescence, controlled proteolysis, size-exclusion chromatography, and multi-angle light scattering showed that it is a properlyfolded monomeric domain. Equilibrium experiments, in the presence of guanidinium chloride and thermal unfolding, suggest a two-state mechanism with a ΔG of 2.3-3.3 kcal/mol, respectively. The study establishes common features and differences of MPE phogrin and the homologous ectodomain of ICA512. A homology model of phogrin was built based in the x-ray structure of MPE ICA512. The model is a starting point for modeling the entire receptor and for testing the quaternary structure and interactions of this protein in vivo. A description of the membrane insertion mode and putative interacting surfaces of this large protein is fundamental for the understanding of its biological function.
Keywords: Diabetes, equilibrium unfolding, homology modeling, phogrin, receptor-type protein-tyrosine phosphatase, secretory granule.
Protein & Peptide Letters
Title:Biophysical Characterization of the Membrane-proximal Ectodomain of the Receptor-type Protein-tyrosine Phosphatase Phogrin
Volume: 20 Issue: 9
Author(s): Martin E. Noguera, Maria E. Primo, Laura N. F. Sosa, Valeria A. Risso, Edgardo Poskus and Mario R. Ermacora
Affiliation:
Keywords: Diabetes, equilibrium unfolding, homology modeling, phogrin, receptor-type protein-tyrosine phosphatase, secretory granule.
Abstract: The receptor-type protein-tyrosine phosphatase (RPTP) phogrin is localized at the membrane of secretory granules of pancreatic islet β-cells and, similarly to the closely related ICA512, plays a role in the regulation of insulin secretion, in ensuring proper granulogenesis and stability, and in the regulation of β-cell growth. The mature membraneproximal ectodomain of phogrin (MPE phogrin) was produced as a recombinant protein and characterized. CD, fluorescence, controlled proteolysis, size-exclusion chromatography, and multi-angle light scattering showed that it is a properlyfolded monomeric domain. Equilibrium experiments, in the presence of guanidinium chloride and thermal unfolding, suggest a two-state mechanism with a ΔG of 2.3-3.3 kcal/mol, respectively. The study establishes common features and differences of MPE phogrin and the homologous ectodomain of ICA512. A homology model of phogrin was built based in the x-ray structure of MPE ICA512. The model is a starting point for modeling the entire receptor and for testing the quaternary structure and interactions of this protein in vivo. A description of the membrane insertion mode and putative interacting surfaces of this large protein is fundamental for the understanding of its biological function.
Export Options
About this article
Cite this article as:
Noguera E. Martin, Primo E. Maria, Sosa N. F. Laura, Risso A. Valeria, Poskus Edgardo and Ermacora R. Mario, Biophysical Characterization of the Membrane-proximal Ectodomain of the Receptor-type Protein-tyrosine Phosphatase Phogrin, Protein & Peptide Letters 2013; 20 (9) . https://dx.doi.org/10.2174/0929866511320090007
DOI https://dx.doi.org/10.2174/0929866511320090007 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
- 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
-
Current Treatment Strategies for Non-Alcoholic Fatty Liver Disease (NAFLD)
Current Drug Discovery Technologies Endothelial Dysfunction in Heart Failure: Mechanisms and Therapeutic Approaches
Current Vascular Pharmacology Central Insulin and Insulin-Like Growth Factor-1 Signaling - Implications for Diabetes Associated Dementia
Current Diabetes Reviews Cardiovascular Complications of Sleep Disorders: A Better Night’s Sleep for a Healthier Heart / From Bench to Bedside
Current Vascular Pharmacology Can Increased Food Intake Improve Psychosis? A Brief Review and Hypothesis
Current Molecular Pharmacology Factor VIII Levels are Associated with Ischemic Stroke, Stroke Subtypes and Neurological Worsening
Current Neurovascular Research SIRT1, a Calorie Restriction Mimetic, in a New Therapeutic Approach for Type 2 Diabetes Mellitus and Diabetic Vascular Complications
Endocrine, Metabolic & Immune Disorders - Drug Targets Current Understanding of Dietary Polyphenols and their Role in Health and Disease
Current Nutrition & Food Science The Patient-centered Medical Home as an Intervention Strategy for Diabetes Mellitus: A Systematic Review of the Literature
Current Diabetes Reviews Risk of Vertical HIV Transmission Combines the ‘B35-Cw4 Disadvantage’ and the ‘Pattern of Inheritance’ Theories of Progression
Current HIV Research Breastfeeding and Diabetes
Current Diabetes Reviews Vascular Endothelial Cell Growth Factor (VEGF), An Emerging Target for Cancer Chemotherapy
Current Medicinal Chemistry - Anti-Cancer Agents Correlation of Waist to Calf Circumference Ratio and Carotid Intima-Media Thickness in Diabetes Mellitus
Current Diabetes Reviews Therapeutic Approaches Using Riboflavin in Mitochondrial Energy Metabolism Disorders
Current Drug Targets Stroke Prevention: From Available Antiplatelet Drugs to Novel Molecular Targets
Current Drug Targets Obstructive Sleep Apnea and Type 2 Diabetes: Dual Interaction
Current Respiratory Medicine Reviews Development of Sol-Gel Hybrid Materials for Whole Cell Immobilization
Recent Patents on Biotechnology Involvement of the Toxic AGEs (TAGE)-RAGE System in the Pathogenesis of Diabetic Vascular Complications: A Novel Therapeutic Strategy
Current Drug Targets Recent Updates on Glucokinase Activators for the Treatment of Type 2 Diabetes Mellitus
Mini-Reviews in Medicinal Chemistry A Magnetic Resonance Spectroscopy Study of Lovastatin for Treating Bipolar Mood Disorder: A 4-Week Randomized Double-Blind, Placebo- Controlled Clinical Trial
Recent Patents on Inflammation & Allergy Drug Discovery