title: Structural basis for the conformational adaptability of apolipophorin III, a helix-bundle exchangeable apolipoprotein.
abstract: The high-resolution NMR structure of apolipophorin III from the sphinx moth, Manduca sexta, has been determined in the lipid-free state. We show that lipid-free apolipophorin III adopts a unique helix-bundle topology that has several characteristic structural features. These include a marginally stable, up-and-down helix bundle that allows for concerted opening of the bundle about "hinged" loops upon lipid interaction and buried polar/ionizable residues and buried interhelical H-bonds located in the otherwise hydrophobic interior of the bundle that adjust protein stability and facilitate lipid-induced conformational opening. We suggest that these structural features modulate the conformational adaptability of the lipid-free helix bundle upon lipid binding and control return of the open conformation to the original lipid-free helix-bundle state. Taken together, these data provide a structural rationale for the ability of exchangeable apolipoproteins to reversibly interact with circulating lipoprotein particles.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Southern Illinois University, Carbondale, IL 62901-4413, USA. jwang@siumed.edu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wang
authors.forename: Brian D
authors.initials: BD
authors.lastname: Sykes
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ryan
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry*; D001665:Binding Sites; D006860:Hydrogen Bonding; D019476:Insect Proteins / Q000737:chemistry; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D018402:Manduca / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013499:Surface Properties
chemical_list: D001053:Apolipoproteins; D019476:Insect Proteins; D008055:Lipids; C042470:apolipophorin III