Abstract
MiRP1 (encoded by the KCNE2 gene) is one of a family of five single transmembrane domain voltage-gated potassium (Kv) channel ancillary subunits currently under intense scrutiny to establish their position in channel complexes and elucidate α subunit contact points, but its structure is unknown. MiRP1 mutations are associated with inherited and acquired cardiac arrhythmia. Here, synthetic peptides corresponding to human MiRP1 (full-length and separate domains) were structurally analyzed using FTIR and CD spectroscopy. The N-terminal (extracellular) domain was soluble and predominantly non-ordered in aqueous media, but predominantly α-helical in L-α-lysophosphatidylcholine (LPC) micelles. The MiRP1 transmembrane domain was predominantly a mixture of α-helix and non-ordered structure in LPC micelles, with a minor contribution from non-aggregated β-strand. The intracellular C-terminal domain was insoluble in aqueous solution; reconstitution into non-aqueous environments resulted in solubility and adoption of increasing amounts of α-helix, with the solvent order sodium dodecyl sulphate < dimyristoyl L-α-phosphatidylcholine (DMPC) < LPC < trifluoroethanol. Correlation of secondary structure changes with lipid transition temperature during heating suggested that the MiRP1 C-terminus incorporates into DMPC bilayers. Full-length MiRP1 was soluble in SDS micelles and calculated to contain 34% α-helix, 23% β-strand and 43% non-ordered structure in this environment, as determined by CD spectroscopy. Thus, MiRP1 is highly dependent upon hydrophobic interaction via lipid and/or protein contacts for adoption of ordered structure without nonspecific aggregation, consistent with a role as a membrane-spanning subunit within Kv channel complexes. These data will provide a structural framework for ongoing mutagenesis-based in situ structure-function studies of MiRP1 and its relatives.
Keywords: KCNE2, HERG, cardiac arrhythmia, FTIR spectroscopy, potassium channel
Protein & Peptide Letters
Title: Secondary Structure of the MiRP1 (KCNE2) Potassium Channel Ancillary Subunit
Volume: 15 Issue: 1
Author(s): G. W. Abbott, B. Ramesh and S. K.S. Srai
Affiliation:
Keywords: KCNE2, HERG, cardiac arrhythmia, FTIR spectroscopy, potassium channel
Abstract: MiRP1 (encoded by the KCNE2 gene) is one of a family of five single transmembrane domain voltage-gated potassium (Kv) channel ancillary subunits currently under intense scrutiny to establish their position in channel complexes and elucidate α subunit contact points, but its structure is unknown. MiRP1 mutations are associated with inherited and acquired cardiac arrhythmia. Here, synthetic peptides corresponding to human MiRP1 (full-length and separate domains) were structurally analyzed using FTIR and CD spectroscopy. The N-terminal (extracellular) domain was soluble and predominantly non-ordered in aqueous media, but predominantly α-helical in L-α-lysophosphatidylcholine (LPC) micelles. The MiRP1 transmembrane domain was predominantly a mixture of α-helix and non-ordered structure in LPC micelles, with a minor contribution from non-aggregated β-strand. The intracellular C-terminal domain was insoluble in aqueous solution; reconstitution into non-aqueous environments resulted in solubility and adoption of increasing amounts of α-helix, with the solvent order sodium dodecyl sulphate < dimyristoyl L-α-phosphatidylcholine (DMPC) < LPC < trifluoroethanol. Correlation of secondary structure changes with lipid transition temperature during heating suggested that the MiRP1 C-terminus incorporates into DMPC bilayers. Full-length MiRP1 was soluble in SDS micelles and calculated to contain 34% α-helix, 23% β-strand and 43% non-ordered structure in this environment, as determined by CD spectroscopy. Thus, MiRP1 is highly dependent upon hydrophobic interaction via lipid and/or protein contacts for adoption of ordered structure without nonspecific aggregation, consistent with a role as a membrane-spanning subunit within Kv channel complexes. These data will provide a structural framework for ongoing mutagenesis-based in situ structure-function studies of MiRP1 and its relatives.
Export Options
About this article
Cite this article as:
Abbott W. G., Ramesh B. and Srai K.S. S., Secondary Structure of the MiRP1 (KCNE2) Potassium Channel Ancillary Subunit, Protein & Peptide Letters 2008; 15 (1) . https://dx.doi.org/10.2174/092986608783330413
DOI https://dx.doi.org/10.2174/092986608783330413 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |

- 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
-
Tissue Engineering for Post-Myocardial Infarction Ventricular Remodeling
Mini-Reviews in Medicinal Chemistry The Glitter of Carbon Nanostructures in Hybrid/Composite Hydrogels for Medicinal Use
Current Topics in Medicinal Chemistry Coffee and Caffeine Effects on Hypertension
Current Hypertension Reviews Contribution of ALDH2 Polymorphism to Alcoholism-Associated Hypertension
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Chronic Obstructive Pulmonary Disease and Sleep Disordered Breathing - The Overlap Syndrome: An Evolving Clinical Phenotype
Current Respiratory Medicine Reviews Pharmacogenetics and Anaesthesiology
Current Pharmacogenomics Clinical and Pre-clinical Applications of the Transcendental Meditation Program® in the Prevention and Treatment of Essential Hypertension and Cardiovascular Disease in Youth and Adults
Current Hypertension Reviews Overcoming hERG Affinity in the Discovery of Maraviroc; A CCR5 Antagonist for the Treatment of HIV
Current Topics in Medicinal Chemistry Association of Viruses in the Development of Cardiovascular Diseases
Current Pharmaceutical Design Bleeding, Vertebral Fractures and Vascular Calcifications in Patients Treated with Warfarin: Hope for Lower Risks with Alternative Therapies
Current Vascular Pharmacology Potassium Channels are a New Target Field in Anticancer Drug Design
Recent Patents on Anti-Cancer Drug Discovery The Digenea Parasite Opisthorchis felineus: A Target for the Discovery and Development of Novel Drugs
Infectious Disorders - Drug Targets Chest Pain, Panic Disorder and Coronary Artery Disease: A Systematic Review
CNS & Neurological Disorders - Drug Targets Update to Medicinal Chemistry of Nicotinamide in the Treatment of Ischemia and Reperfusion
Medicinal Chemistry Reviews - Online (Discontinued) Clinical Implications of Recent Insights into the Structural Biology of Beta2 Adrenoceptors
Current Drug Targets Biologic Agents in the Treatment of Psoriasis
Recent Patents on Inflammation & Allergy Drug Discovery First Comprehensive Analysis of Outcomes in Adult Patients after Percutaneous Closure of Isolated Secundum Atrial Septal Defects
Cardiovascular & Hematological Agents in Medicinal Chemistry Antibiotics with Antiviral and Anti-Inflammatory Potential Against Covid-19: A Review
Current Reviews in Clinical and Experimental Pharmacology Need for Ongoing Anti Arrhythmic Drugs After Ablation of Atrial Fibrillation. Review
Recent Patents on Cardiovascular Drug Discovery Risk Stratification for Sudden Cardiac Death: Current Approaches and Predictive Value
Current Cardiology Reviews