title: The structure of dimeric apolipoprotein A-IV and its mechanism of self-association.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, College of Medicine, University of Cincinnati, OH 45267, USA.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Deng
authors.forename: Jamie
authors.initials: J
authors.lastname: Morris
authors.forename: James
authors.initials: J
authors.lastname: Dressmen
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Tubb
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
authors.forename: W Gray
authors.initials: WG
authors.lastname: Jerome
authors.forename: W Sean
authors.initials: WS
authors.lastname: Davidson
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Thompson
mesh_terms: D001054:Apolipoproteins A / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D050356:Lipid Metabolism; D008958:Models, Molecular; D017433:Protein Structure, Secondary
chemical_list: D001054:Apolipoproteins A; C022205:apolipoprotein A-IV