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Journal of Lipid Research, Vol. 49, 1875-1883, September 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Review

Three-dimensional models of HDL apoA-I: implications for its assembly and function^*

Michael J. Thomas^*, Shaila Bhat and Mary G. Sorci-Thomas^1,*,

^* Department of Biochemistry, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157
Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157

^* These studies were supported by The National Heart, Lung, and Blood Institute, National Institutes of Health (Grants HL-49373 and HL-64163 to M.G.S-T.) and an International HDL Pfizer Award to M.J.T.

Published, JLR Papers in Press, May 30, 2008.

¹ To whom correspondence should be addressed. e-mail: msthomas{at}wfubmc.edu

The purpose of this review is to highlight recent advances toward the refinement of a three-dimensional structure for lipid-bound apolipoprotein A-I (apoA-I) on recombinant HDL. Recently, X-ray crystallography has yielded a new structure for full-length, lipid-free apoA-I. Although this approach has not yet been successful in solving the three-dimensional structure of lipid-bound apoA-I, analysis of the X-ray structures has been of immense help in the interpretation of structural data obtained from other methods that yield structural information. Recent studies emphasize the use of mass spectrometry to unambiguously identify cross-linked peptides or to quantify solvent accessibility using hydrogen-deuterium exchange. The combination of mass spectrometry, molecular modeling, molecular dynamic analysis, and small-angle X-ray diffraction has provided additional structural information on apoA-I folding that complements previous approaches.

Supplementary key words cholesterol • mass spectrometry • hydrogen-deuterium exchange • molecular dynamic modeling • chemical cross-linking • apolipoprotein A-I

Abbreviations: AEDANS, N-(iodoacetyl)'-(5-sulfo-1-naphthyl)ethylenediamine; apoA-I, apolipoprotein A-I; CCL/MS, chemical cross-linking/mass spectrometry; DMPC, 1,2-dimysteroyl-sn-glycerol-3-phosphocholine; DPPC, 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine; FRET, fluorescence resonance energy transfer; H/DX, hydrogen-deuterium exchange; POPC, 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine; rHDL, recombinant HDL; SAXS, small-angle X-ray scattering

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