Although fundamentally significant in structural, chemical, and membrane biology,
the interfacial protein-detergent complex (PDC) interactions have been modestly examined
because of the complicated behavior of both detergents and membrane proteins in aqueous
phase. Membrane proteins are prone to unproductive aggregation resulting from poor
detergent solvation, but the participating forces in this phenomenon remain ambiguous.
Here, we show that using rational membrane protein design, targeted chemical modification,
and steady-state fluorescence polarization spectroscopy, the detergent desolvation of
membrane proteins can be quantitatively evaluated. We demonstrate that depleting the
detergent in the sample well produced a two-state transition of membrane proteins between
a fully detergent-solvated state and a detergent-desolvated state, the nature of which
depended on the interfacial PDC interactions. Using a panel of six membrane proteins of
varying hydrophobic topography, structural fingerprint, and charge distribution on the
solvent-accessible surface, we provide direct experimental evidence for the contributions
of the electrostatic and hydrophobic interactions to the protein solvation properties.
Moreover, all-atom molecular dynamics simulations report the major contribution of the
hydrophobic forces exerted at the PDC interface. This semi-quantitative approach might be
extended in the future to include studies of the interfacial PDC interactions of other
challenging membrane protein systems of unknown structure. This would have practical
importance in protein extraction, solubilization, stabilization, and crystallization.
Hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage, and over the past several decades, many researchers have worked to develop novel effective therapies for HCC patients. The functional contributions of mesenchymal stem cells to human malignancies, including HCC growth and progression, are controversial, and the potential mechanisms underlying these effects are not clear. The aim of this study was to investigate the effect of adipose-derived mesenchymal stem cells (ADSCs) on the growth of HCC cells. In this study, a conditioned medium from ADSCs (ADSC-CM) efficiently inhibited HCC cell proliferation and division, and induced HCC cell death through the downregulation of Akt signaling. These findings indicated that the ADSC-CM could inhibit HCC growth. Thus, the ADSC-CM is a good candidate for the treatment of HCC patients for whom no effective therapy is available.
Selenoprotein K (SelK) is a membrane protein involved in antioxidant defense, calcium regulation and the ER-associated protein degradation pathway. We found that SelK exhibits a peroxidase activity with a rate that is low but within the range of other peroxidases. Notably, SelK reduced hydrophobic substrates, such as phospholipid hydroperoxides, which damage membranes. Thus, SelK might be involved in membrane repair or related pathways. SelK was also found to contain a diselenide bond — the first intramolecular bond of that kind reported for a selenoprotein. The redox potential of SelK was −257 mV, significantly higher than that of diselenide bonds in small molecules or proteins. Consequently, SelK can be reduced by thioredoxin reductase. These finding are essential for understanding SelK activity and function.
Hepatic stellate cells (HSCs) have immunosuppressive capabilities and contribute to the occurrence and development of hepatocellular carcinoma (HCC). Thus, activated HSCs may be a suitable target for HCC therapy. Our study used mixed leukocyte reactions (MLR) in vitro to demonstrate that 18β‐glycyrrhetinic acid (GA) could reverse HSC‐mediated immunosuppression by reducing T‐cell apoptosis and regulatory T (Treg) cells expression, thereby enhancing the ability of T cells to attack tumor cells and attenuating HCC cell invasiveness. Moreover, we established a HCC orthotopic implantation model in immunocompetent C57BL/6 mice, which suggested that GA played a protective role in HCC development by reducing immunosuppression mediated by HSCs in the tumor microenvironment.
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