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  • Generic structures of cytotoxic liprotides: nano-sized complexes with oleic acid cores and shells of disordered proteins.

Generic structures of cytotoxic liprotides: nano-sized complexes with oleic acid cores and shells of disordered proteins.

Chembiochem : a European journal of chemical biology (2014-11-19)
Jørn D Kaspersen, Jannik N Pedersen, Jon G Hansted, Søren B Nielsen, Srinivasan Sakthivel, Kristina Wilhelm, Ekaterina L Nemashkalova, Sergei E Permyakov, Eugene A Permyakov, Cristiano Luis Pinto Oliveira, Ludmilla A Morozova-Roche, Daniel E Otzen, Jan Skov Pedersen
ABSTRACT

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.

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