Generic structures of cytotoxic liprotides: nano-sized complexes with oleic acid cores and shells of disordered proteins.
The cytotoxic complex formed between α-lactalbumin and oleic acid (OA) has inspired many studies on protein-fatty acid complexes, but structural insight remains sparse. After having used small-angle X-ray scattering (SAXS) to obtain structural information, we present a new, generic structural model of cytotoxic protein-oleic acid complexes, which we have termed liprotides (lipids and partially denatured proteins). Twelve liprotides formed from seven structurally unrelated proteins and prepared by different procedures all displayed core-shell structures, each with a micellar OA core and a shell consisting of flexible, partially unfolded protein, which stabilizes the OA micelle. The common structure explains similar effects exerted on cells by different liprotides and is consistent with a cargo off-loading of the OA into cell membranes.
Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C (Denmark).
Jørn D
JD
Kaspersen
Jannik N
JN
Pedersen
Jon G
JG
Hansted
Søren B
SB
Nielsen
Srinivasan
S
Sakthivel
Kristina
K
Wilhelm
Ekaterina L
EL
Nemashkalova
Sergei E
SE
Permyakov
Eugene A
EA
Permyakov
Cristiano Luis
CL
Pinto Oliveira
Ludmilla A
LA
Morozova-Roche
Daniel E
DE
Otzen
Jan Skov
JS
Pedersen
D000818:Animals; D002417:Cattle; D003603:Cytotoxins / Q000737:chemistry* / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects; D008823:Micelles; D009829:Oleic Acids / Q000737:chemistry* / Q000494:pharmacology; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000494:pharmacology; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
D003603:Cytotoxins; D008823:Micelles; D009829:Oleic Acids; D011506:Proteins
lipids; micelles; protein folding; protein structures; protein-protein interactions