Membrane-induced folding of the cAMP-regulated phosphoprotein endosulfine-α

John M. Boettcher, Kevin L. Hartman, Daniel T. Ladror, Zhi Qi, Wendy S. Woods, Julia M. George, Chad M. Rienstra

Research output: Contribution to journalArticlepeer-review


Endosulfine-α (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 α-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 α-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 α-synuclein.

Original languageEnglish (US)
Pages (from-to)12357-12364
Number of pages8
Issue number47
StatePublished - Nov 25 2008

ASJC Scopus subject areas

  • Biochemistry


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