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

J. Biol. Chem., Vol. 283, Issue 25, 17314-17323, June 20, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/25/17314    most recent M800036200v1 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 Tubb, M. R. Articles by Davidson, W. S. Search for Related Content PubMed PubMed Citation Articles by Tubb, M. R. Articles by Davidson, W. S. Social Bookmarking                      What's this?

A Three-dimensional Homology Model of Lipid-free Apolipoprotein A-IV Using Cross-linking and Mass Spectrometry^*

Matthew R. Tubb, R. A. Gangani D. Silva, Jianwen Fang, Patrick Tso, and W. Sean Davidson¹

From the Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio 45237 and the Bioinformatics Core Facility, University of Kansas, Lawrence, Kansas 66045

Human apolipoprotein A-IV (apoA-IV) is a 46-kDa exchangeable plasma protein with many proposed functions. It is involved in chylomicron assembly and secretion, protection from atherosclerosis through a variety of mechanisms, and inhibition of food intake. There is little structural basis for these proposed functions due to the lack of a solved three-dimensional structure of the protein by x-ray crystallography or NMR. Based on previous studies, we hypothesized that lipid-free apoA-IV exists in a helical bundle, like other apolipoprotein family members and that regions near the N and C termini may interact. Utilizing a homobifunctional lysine cross-linking agent, we identified 21 intramolecular cross-links by mass spectrometry. These cross-links were used to constrain the building of a sequence threaded homology model using the I-TASSER server. Our results indicate that lipid-free apoA-IV does indeed exist as a complex helical bundle with the N and C termini in close proximity. This first structural model of lipid-free apoA-IV should prove useful for designing studies aimed at understanding how apoA-IV interacts with lipids and possibly with unknown protein partners.

Received for publication, January 2, 2008 , and in revised form, April 10, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grants HL67093 and HL82734 (to W. S. D.). This work was also supported by a predoctoral fellowship from the Great Rivers Affiliate of the American Heart Association (to M. R. T.) and a University of Cincinnati graduate research fellowship (to M. R. T.). 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: Dept. of Pathology and Laboratory Medicine, University of Cincinnati, 2120 Galbraith Rd., Cincinnati, OH 45237-0507. Tel.: 513-558-3707; Fax: 513-558-1312; E-mail: Sean.Davidson{at}UC.edu.

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

This article has been cited by other articles:

				J. B. Massey, H. J. Pownall, S. Macha, J. Morris, M. R. Tubb, and R. A. G. D. Silva Mass spectrometric determination of apolipoprotein molecular stoichiometry in reconstituted high density lipoprotein particles J. Lipid Res., June 1, 2009; 50(6): 1229 - 1236. [Abstract] [Full Text] [PDF]

				T. Vaisar Thematic Review Series: Proteomics. Proteomic analysis of lipid-protein complexes J. Lipid Res., May 1, 2009; 50(5): 781 - 786. [Abstract] [Full Text] [PDF]