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J. Biol. Chem., Vol. 277, Issue 24, 21549-21553, June 14, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/24/21549    most recent M202197200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weinberg, R. B. Articles by Steinmetz, A. Search for Related Content PubMed PubMed Citation Articles by Weinberg, R. B. Articles by Steinmetz, A. Social Bookmarking                      What's this?

Interfacial Exclusion Pressure Determines the Ability of Apolipoprotein A-IV Truncation Mutants to Activate Cholesterol Ester Transfer Protein^*

Richard B. Weinberg^§¶, Rachel A. Anderson, Victoria R. Cook, Florence Emmanuel, Patrice Denèfle^**, Alan R. Tall, and Armin Steinmetz^§§¶¶

From the Departments of  Internal Medicine and ^§ Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, the  Cardiovascular Department, Gencell Division, ^** Functional Genomics Center, Aventis Pharma, 94403 Vitry sur Seine, France, the  Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, and the ^§§ St. Nikolaus Stiftshospital Teaching Hospital, University of Bonn, D-56626 Andernach, Germany

We used a panel of recombinant human apolipoprotein (apo) A-IV truncation mutants, in which pairs of 22-mer -helices were sequentially deleted along the primary sequence, to examine the impact of protein structure and interfacial activity on the ability of apoA-IV to activate cholesterol ester transfer protein. Circular dichroism and fluorescence spectroscopy revealed that the secondary structure, conformation, and molecular stability of recombinant human apoA-IV were identical to the native protein. However, deletion of any of the -helical domains in apoA-IV disrupted its tertiary structure and impaired its molecular stability. Surprisingly, determination of the water/phospholipid interfacial exclusion pressure of the apoA-IV truncation mutants revealed that, for most, deletion of amphipathic -helical domains increased their affinity for phospholipid monolayers. All of the truncation mutants activated the transfer of fluorescent-labeled cholesterol esters between high and low density lipoproteins at a rate higher than native apoA-IV. There was a strong positive correlation (r = 0.790, p = 0.002) between the rate constant for cholesterol ester transfer and interfacial exclusion pressure. We conclude that molecular interfacial exclusion pressure, rather than specific helical domains, determines the degree to which apoA-IV, and likely other apolipoproteins, facilitate cholesterol ester transfer protein-mediated lipid exchange.

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