HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 29, 20418-20426, July 21, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/29/20418    most recent M602077200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Martin, D. D. O. Articles by Oda, M. N. Search for Related Content PubMed PubMed Citation Articles by Martin, D. D. O. Articles by Oda, M. N. Social Bookmarking                      What's this?

Apolipoprotein A-I Assumes a "Looped Belt" Conformation on Reconstituted High Density Lipoprotein^*

Dale D. O. Martin, Madhu S. Budamagunta, Robert O. Ryan, John C. Voss, and Michael N. Oda¹

From the Children's Hospital Oakland Research Institute, Oakland, California 94609-1673 and the Department of Biological Chemistry, University of California, Davis, California 95616

Apolipoprotein A-I (apoA-I) plays a central role in the reverse cholesterol transport pathway; however, the structural basis for its antiatherogenic effects remains poorly understood. Here we employ EPR spectroscopy and fluorescence resonance energy transfer to elucidate the conformation and relative alignment of apoA-I monomers on discoidal (9.4 nm) reconstituted high density lipoprotein (rHDL). EPR spectroscopy provided evidence for an extended helical secondary structure. Position 139 since it was the only residue examined to display a dynamic motional character consistent with a flexible loop structure. The EPR spectra of nitroxide probes at positions 133 and 146 exhibit spin coupling, indicating that these positions are proximal to an apoA-I paired counterpart on the perimeter of rHDL. fluorescence resonance energy transfer studies employing engineered apoA-I variants possessing a single tryptophan (energy donor) and/or a single cysteine (whose thiol moiety was covalently labeled with an extrinsic energy acceptor) provided evidence that paired apoA-I molecules around the perimeter of rHDL align in an extended antiparallel conformation. Taken together with the observation that the EPR spectra of nitroxide probes positioned at intervening sequence positions (134-145) do not exhibit spin coupling, this has led us to propose a "looped belt" model, wherein residues 133-146 comprise a flexible loop segment that confers to apoA-I an intrinsic ability to adapt its structure to accommodate changing particle lipid content. Specifically, in the looped belt model, with the exception of amino acids 134-145, apoA-I aligns with its counterpart in a helix 5-helix 5 registry, centered at position 139.

Received for publication, March 6, 2006 , and in revised form, May 11, 2006.

^* This work was supported by NHLBI, National Institutes of Health (NIH), Grants HL077268 and HL64159 and by American Heart Association Scientist Development Grant 0235222N. This investigation was partially conducted in a facility supported by NIH NCRR Research Facilities Improvement Program Grant C06 RR-12088-01. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Children's Hospital Oakland Research Institute, Oakland, CA 94609-1673. Tel.: 510-450-7652; Fax: 510-450-7920; E-mail: moda{at}chori.org.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. J. Thomas, S. Bhat, and M. G. Sorci-Thomas Three-dimensional models of HDL apoA-I: implications for its assembly and function J. Lipid Res., September 1, 2008; 49(9): 1875 - 1883. [Abstract] [Full Text] [PDF]

				R. A. G. D. Silva, R. Huang, J. Morris, J. Fang, E. O. Gracheva, G. Ren, A. Kontush, W. G. Jerome, K.-A. Rye, and W. S. Davidson Structure of apolipoprotein A-I in spherical high density lipoproteins of different sizes PNAS, August 26, 2008; 105(34): 12176 - 12181. [Abstract] [Full Text] [PDF]

				B. Shao, G. Cavigiolio, N. Brot, M. N. Oda, and J. W. Heinecke Methionine oxidation impairs reverse cholesterol transport by apolipoprotein A-I PNAS, August 26, 2008; 105(34): 12224 - 12229. [Abstract] [Full Text] [PDF]

				R. Carnemolla, X. Ren, T. K. Biswas, S. C. Meredith, C. A. Reardon, J. Wang, and G. S. Getz The Specific Amino Acid Sequence between Helices 7 and 8 Influences the Binding Specificity of Human Apolipoprotein A-I for High Density Lipoprotein (HDL) Subclasses: A POTENTIAL FOR HDL PREFERENTIAL GENERATION J. Biol. Chem., June 6, 2008; 283(23): 15779 - 15788. [Abstract] [Full Text] [PDF]

				G. D. Wool, C. A. Reardon, and G. S. Getz Apolipoprotein A-I mimetic peptide helix number and helix linker influence potentially anti-atherogenic properties J. Lipid Res., June 1, 2008; 49(6): 1268 - 1283. [Abstract] [Full Text] [PDF]

				W. S. Davidson and T. B. Thompson The Structure of Apolipoprotein A-I in High Density Lipoproteins J. Biol. Chem., August 3, 2007; 282(31): 22249 - 22253. [Full Text] [PDF]

				M. Fukuda, M. Nakano, S. Sriwongsitanont, M. Ueno, Y. Kuroda, and T. Handa Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I J. Lipid Res., April 1, 2007; 48(4): 882 - 889. [Abstract] [Full Text] [PDF]

				J. O. Lagerstedt, M. S. Budamagunta, M. N. Oda, and J. C. Voss Electron Paramagnetic Resonance Spectroscopy of Site-directed Spin Labels Reveals the Structural Heterogeneity in the N-terminal Domain of ApoA-I in Solution J. Biol. Chem., March 23, 2007; 282(12): 9143 - 9149. [Abstract] [Full Text] [PDF]