title: Small-angle X-ray scattering of BAMLET at pH 12: a complex of α-lactalbumin and oleic acid.
abstract: BAMLET (Bovine Alpha-lactalbumin Made LEthal to Tumors) is a member of the family of the HAMLET-like complexes, a novel class of protein-based anti-cancer complexes that incorporate oleic acid and deliver it to cancer cells. Small angle X-ray scattering (SAXS) was performed on the complex at pH 12, examining the high pH structure as a function of oleic acid added. The SAXS data for BAMLET species prepared with a range of oleic acid concentrations indicate extended, irregular, partially unfolded protein conformations that vary with the oleic acid concentration. Increases in oleic acid concentration correlate with increasing radius of gyration without an increase in maximum particle dimension, indicating decreasing protein density. The models for the highest oleic acid content BAMLET indicate an unusual coiled elongated structure that contrasts with apo-α-lactalbumin at pH 12, which is an elongated globular molecule, suggesting that oleic acid inhibits the folding or collapse of the protein component of BAMLET to the globular form. Circular dichroism of BAMLET and apo-α-lactalbumin was performed and the results suggest that α-lactalbumin and BAMLET unfold in a continuum of increasing degree of unfolded states. Taken together, these results support a model in which BAMLET retains oleic acid by non-specific association in the core of partially unfolded protein, and represent a new type of lipoprotein structure.
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, 2006, Australia.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Rath
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Duff
authors.forename: Anders P
authors.initials: AP
authors.lastname: Håkansson
authors.forename: Robert B
authors.initials: RB
authors.lastname: Knott
authors.forename: W Bret
authors.initials: WB
authors.lastname: Church
mesh_terms: D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D007768:Lactalbumin / Q000737:chemistry*; D008958:Models, Molecular; D019301:Oleic Acid / Q000737:chemistry*; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: C560443:BAMLET complex, Bos taurus; D019301:Oleic Acid; D007768:Lactalbumin
keywords: BAMLET; HAMLET; SAXS; circular dichroism; lipid-binding protein; lipoprotein; oleic acid; partially unfolded protein; protein-fatty acid complex; α-lactalbumin