Apolipoprotein A-I lysine modification: Effects on helical content, lipid binding and cholesterol acceptor activity

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• 作者：Gregory Brubaker ; Dao-Quan Peng ; Benjamin Somerlot ; Davood J. Abdollahian and Jonathan D. Smith
• 关键词：Reverse cholesterol transport ; Lipid binding ; Class A amphipathic helix ; Circular dichroism ; Alpha helical content
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2006
• 出版时间：January 2006
• 年：2006
• 卷：1761
• 期：1
• 页码：64-72
• 全文大小：419 K

文摘

We examined the role of the positively charged lysine residues in apoAI by chemical modification. Lysine modification by reductive methylation did not alter apoAI's net charge, secondary or tertiary structure as observed by circular dichroism and trytophan fluorescence, respectively, or have much impact on lipid binding or ABCA1-dependent cholesterol acceptor activity. Acetylation of lysine residues lowered the isoelectric point of apoAI, altered its secondary and tertiary structure, and led to a 40 % decrease in cholesterol acceptor activity, while maintaining 93 % of its lipid binding activity. Exhaustive lysine acetoacetylation lowered apoAI's isoelectric point, profoundly disrupted its secondary and tertiary structure, and led to 90 % and 82 % reductions in cholesterol acceptor and lipid binding activities, respectively. The dose-dependent acetoacetylation of an increasing proportion of apoAI lysine residues demonstrated that cholesterol acceptor activity was more sensitive to this modification than lipid binding activity, suggesting that apoAI lysine positive charges play an important role in ABCA1 mediated lipid efflux beyond the role needed to maintain α-helical content and lipid binding activity.