27 research outputs found
Cationic Liposomes Target Sites of Acute Neuroinflammation in Experimental Autoimmune Encephalomyelitis
The contribution of aquatic ecosystems and fisheries to food security and livelihoods: a research agenda. Challenge Program on Water and Food background paper 3
In CGIAR Challenge Program on Water and Food. Challenge Program on Water and Food: background papers to the full proposal. Colombo, Sri Lanka: CGIAR Challenge Program on Water and Food
Contributions of a disulfide bond and a reduced cysteine side chain to the intrinsic activity of the HDL receptor SR-BI
The high density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), binds HDL and mediates selective cholesteryl ester uptake. SR-BI's structure and mechanism are poorly understood. We used mass spectrometry to assign the two disulfide bonds in SR-BI that connect cysteines within the conserved Cys[superscript 321]-Pro[superscript 322]-Cys[superscript 323] (CPC) motif and connect Cys[superscript 280] to Cys[superscript 334]. We used site-specific mutagenesis to evaluate the contributions of the CPC motif and the side chain of extracellular Cys[superscript 384] to HDL binding and lipid uptake. The effects of CPC mutations on activity were context dependent. Full wild-type (WT) activity required Pro[superscript 322] and Cys[superscript 323] only when Cys[superscript 321] was present. Reduced intrinsic activities were observed for CXC and CPX, but not XXC, XPX or XXX mutants (X≠WT residue). Apparently, a free thiol side chain at position 321 that cannot form an intra-CPC disulfide bond with Cys[superscript 323] is deleterious, perhaps because of aberrant disulfide bond formation. Pro[superscript 322] may stabilize an otherwise strained CPC disulfide bond, thus supporting WT activity, but this disulfide bond is not absolutely required for activity. C[superscript 384]X (X=S,T,L,Y,G,A) mutants exhibited altered activities that varied with the side chain's size: larger side chains phenocopied WT SR-BI treated with its thiosemicarbazone inhibitor BLT-1 (increased binding, decreased uptake); smaller side chains produced almost inverse effects (increased uptake:binding ratio). C[superscript 384]X mutants were BLT-1 resistant, supporting the proposal that Cys[superscript 384]'s thiol interacts with BLT-1. We discuss the implications of our findings on the functions of the extracellular loop cysteines in SR-BI and compare our results to those presented by other laboratories.National Institutes of Health (U.S.) (Grant HL052212)National Institutes of Health (U.S.) (Grant HL066105)National Institutes of Health (U.S.) (Graduate Student Training Grant 5-T32-GM007287)Susan G. Komen Breast Cancer Foundatio
Sportswomen in the German popular press: a study carried out in the context of the 2011 Women’s Football World Cup
Unlocking the licence of power? The political system of FIFA and the constraints of opposition and protest in international sport federations
Tubular structures in affected and normal skin in chronic discoid and systemic lupus erythematosus: electron microscopic studies
gp96-Peptide Vaccination of Mice against Intracellular Bacteria
This work demonstrates that gp96 preparations isolated from cells infected with intracellular bacteria induce cytotoxic T-lymphocyte responses and confer protection. Our findings extend previous reports on the immunogenicity of gp96-associated peptides to antigens derived from intracellular bacteria. Immunization with gp96 may therefore represent a promising vaccination strategy against bacterial pathogens