Surface tensiometry of apolipoprotein B domains at lipid interfaces suggests a new model for the initial steps in triglyceride-rich lipoprotein assembly. [Membrane Biology]

February 10th, 2014 by Mitsche, M. A., Packer, L. E., Brown, J. W., Jiang, Z. G., Small, D. M., McKnight, C. J.

Apolipoprotein B (ApoB) is the principal protein component of triacylglyceride (TAG)-rich lipoproteins, including chylomicrons and very low density lipoprotein which is the precursor to LDL (the "bad-cholesterol"). TAG-rich lipoprotein assembly is initiated by the N-terminal βα1 super-domain of ApoB, which co-translationally binds and remodels the luminal leaflet of the rough endoplasmic reticulum (ER). The βα1 super-domain contains four domains and is predicted to interact directly with lipids. Using drop tensiometry, we examined the interfacial properties of the α-helical and C-Sheet domains, and several sub-domains to establish a detailed structure-function relationship at the lipid/water interface. The adsorption, stress response, exchangeability, and pressure Π area relationship were studied at both triolein/water (TO/W) and TO/palmitoyl, oleoyl phosphatidylcholine (POPC)/W interfaces that mimic physiological environments. The -α helical domain spontaneously adsorbed to a TO/W interface and formed a viscoelastic surface. It was anchored to the surface by helix 6 and the other helices were ejected and/or remodeled on the surface as a function of surface pressure. The C-Sheet instead formed an elastic film on a TO/W interface and was irreversibly anchored to the lipid surface which is consistent with the behavior of amphipathic -β-strands. When both domains were adsorbed together to the surface, the C-Sheet shielded a portion of the α-helical domain from the surface, which retained its globular structure. Overall, the unique secondary and tertiary structure of the N-terminal domains of ApoB support the intrinsic capability of co-translational lipid recruitment. The evidence here allows the construction of a detailed model of the initiation of TAG-rich lipoprotein assembly.
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