Structure and lipid interactions of an anti-inflammatory and anti-atherogenic 10-residue class G apolipoprotein J peptide using solution NMR

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• 作者：Vinod K. Mishra ; Mayakonda N. Palgunachari ; Jason S. Hudson ; Ronald Shin ; Tamara D. Keenum ; N. Rama Krishna ; G.M. Anantharamaiah
• 关键词：Apolipoprotein J ; Class G* helix ; Peptide ; Dodecylphosphocholine micelle ; Oxidized lipid ; 1-Palmitoyl-2-(5-keto-6-octene dioyl)phosphatidylcholine ; Nuclear magnetic resonance spectroscopy ; Isothermal titration calorimetry ; Circular dichroism
• 刊名：Biochimica et Biophysica Acta (BBA)/Biomembranes
• 出版年：2011
• 出版时间：January 2011
• 年：2011
• 卷：1808
• 期：1
• 页码：498-507
• 全文大小：1088 K

文摘

The surprising observation that a 10-residue class G peptide from apolipoprotein J, [113–122]apoJ, possesses anti-inflammatory and anti-atherogenic properties prompted us to delineate its structural characteristics in the presence of normal and oxidized lipid. Towards this, we have determined high-resolution structure of [113–122]apoJ in solution using nuclear magnetic resonance (NMR) spectroscopy and studied its interaction with lipids, including oxidized lipids, using a number of biophysical methods. Circular dichroism and NMR studies established that in the presence of dodecylphosphocholine (DPC) micelle, this peptide adopts amphipathic α-helical structure. The observed Nuclear Overhauser effects indicate that the amphipathic helical structure of the peptide is stabilized by the N-terminal acetyl and C-terminal amide blocking groups. We used isothermal titration calorimetry to measure binding enthalpy of the peptide with DPC micelle, an oxidized lipid, 1-(palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdiA-PC), and the mixture of these two lipids (5 mol % KOdiA-PC in DPC micelle). We find that the peptide binding with DPC micelle is associated with an enthalpy change (−16.75 ± 0.16 Kcal/mol) much larger than that resulting from the binding with KodiA-PC (−3.67 ± 0.13 Kcal/mol). Incorporation of a small amount of KOdiA-PC (5 mol % ) in DPC micelle also results in the lowering of peptide binding enthalpy (−13.43 ± 0.18 Kcal/mol). These results are consistent with overall negative charge and altered conformational properties of oxidized sn-2 chain of KOdiA-PC. Our results have unambiguously established the amphipathic α-helical structure of [113–122]apoJ peptide in the presence of DPC micelle as well as its ability to bind oxidized lipid. These in vitro results help explain the previously observed anti-inflammatory and anti-atherosclerotic properties of this peptide.