Membrane-induced folding of the cAMP-regulated phosphoprotein endosulfine-alpha
| Autor: | Wendy S. Woods, Jimin George, Kevin L. Hartman, Daniel T. Ladror, Chad M. Rienstra, Zhi Qi, John M. Boettcher |
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| Rok vydání: | 2008 |
| Předmět: |
Conformational change
Protein Folding Magnetic Resonance Spectroscopy Inositol Phosphates Biology Biochemistry Protein Structure Secondary chemistry.chemical_compound Biomimetic Materials Sodium dodecyl sulfate Phosphorylation Micelles Phospholipids Phosphocholine Phosphatidylglycerol Circular Dichroism Cell Membrane Sodium Dodecyl Sulfate Phosphoproteins Cyclic AMP-Dependent Protein Kinases Potassium channel Cell biology Membrane chemistry Phosphoprotein Helix Chromatography Gel alpha-Synuclein Intercellular Signaling Peptides and Proteins lipids (amino acids peptides and proteins) Glycolipids Peptides Protein Binding |
| Zdroj: | Biochemistry. 47(47) |
| ISSN: | 1520-4995 |
| Popis: | Endosulfine-alpha (ENSA) is a 121-residue cAMP-regulated phosphoprotein, originally identified as an endogenous regulator of ATP-sensitive potassium channels. ENSA has been implicated in the regulation of insulin secretion, and expression of ENSA is decreased in brains of both Alzheimer's disease (AD) and Down's syndrome patients. We recently described membrane-dependent interactions between ENSA and the Parkinson's disease associated protein alpha-synuclein. Here we characterize the conformational change in ENSA that occurs upon binding to membranes. Secondary chemical shift analysis demonstrates formation of four helices in the lipid-bound state that are not present in the absence of lipid. The helical structure is maintained in several different lipid mimetics (sodium dodecyl sulfate, dodecyl phosphocholine, lyso 1-palmitoyl phosphatidylglycerol, and phospholipid vesicles). Introduction of a mutation (S109E) to mimic PKA phosphorylation of ENSA leads to a perturbation of the fourth helix and disrupts the interaction with alpha-synuclein. These data establish ENSA as an intrinsically unstructured protein that adopts a stable structure upon membrane binding, properties it shares with its binding partner alpha-synuclein. |
| Databáze: | OpenAIRE |
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