The structure of dimeric apolipoprotein A-IV and its mechanism of self-association.

Deng X, Morris J, Dressmen J, Tubb MR, Tso P, Jerome WG, Davidson WS, Thompson TB
Structure. 2012 20 (5): 767-79

PMID: 22579246 · PMCID: PMC3354570 · DOI:10.1016/j.str.2012.02.020

Apolipoproteins are key structural elements of lipoproteins and critical mediators of lipid metabolism. Their detergent-like properties allow them to emulsify lipid or exist in a soluble lipid-free form in various states of self-association. Unfortunately, these traits have hampered high-resolution structural studies needed to understand the biogenesis of cardioprotective high-density lipoproteins (HDLs). We derived a crystal structure of the core domain of human apolipoprotein (apo)A-IV, an HDL component and important mediator of lipid absorption. The structure at 2.4 Å depicts two linearly connected 4-helix bundles participating in a helix swapping arrangement that offers a clear explanation for how the protein self-associates as well as clues to the structure of its monomeric form. This also provides a logical basis for antiparallel arrangements recently described for lipid-containing particles. Furthermore, we propose a "swinging door" model for apoA-IV lipid association.

Copyright © 2012 Elsevier Ltd. All rights reserved.

MeSH Terms (8)

Apolipoproteins A Binding Sites Crystallography, X-Ray Dimerization Humans Lipid Metabolism Models, Molecular Protein Structure, Secondary

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