Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

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Free and polymerized tubulin in cultured bone cells and Chinese hamster ovary cells: the influence of cold and hormones

A low pH method of liposome-membrane fusion (Schneider et al., 1980, Proc. Natl. Acad. Sci. U. S. A. 77:442) was used to enrich the mitochondrial inner membrane lipid bilayer 30-700% with exogenous phospholipid and cholesterol. By varying the phospholipid-to- cholesterol ratio of the liposomes it was possible to incorporate specific amounts of cholesterol (up to 44 mol %) into the inner membrane bilayer in a controlled fashion. The membrane surface area increased proportionally to the increase in total membrane bilayer lipid. Inner membrane enriched with phospholipid only, or with phospholipid plus cholesterol up to 20 mol %, showed randomly distributed intramembrane particles (integral proteins) in the membrane plane, and the average distance between intramembrane particles increased proportionally to the amount of newly incorporated lipid. Membranes containing between 20 and 27 mol % cholesterol exhibited small clusters of intramembrane particles while cholesterol contents above 27 mol % resulted in larger aggregations of intramembrane particles. In phospholipid-enriched membranes with randomly dispersed intramembrane particles, electron transfer activities from NADH- and succinate-dehydrogenase to cytochrome c decreased proportionally to the increase in distance between the particles. In contrast, these electron- transfer activities increased with decreasing distances between intramembrane particles brought about by cholesterol incorporation. These results indicate that (a) catalytically interacting redox components in the mitochondrial inner membrane such as the dehydrogenase complexes, ubiquinone, and heme proteins are independent, laterally diffusible components; (b) the average distance between these redox components is effected by the available surface area of the membrane lipid bilayer; and (c) the distance over which redox components diffuse before collision and electron transfer mediates the rate of such transfer.     

OGR1/GPR68 Modulates the Severity of Experimental Autoimmune Encephalomyelitis and Regulates Nitric Oxide Production by Macrophages

Ovarian cancer G protein-coupled receptor 1 (OGR1) is a proton-sensing molecule that can detect decreases in extracellular pH that occur during inflammation. Although OGR1 has been shown to have pro-inflammatory functions in various diseases, its role in autoimmunity has not been examined. We therefore sought to determine whether OGR1 has a role in the development of T cell autoimmunity by contrasting the development of experimental autoimmune encephalomyelitis between wild type and OGR1-knockout mice. OGR1-knockout mice showed a drastically attenuated clinical course of disease that was associated with a profound reduction in the expansion of myelin oligodendrocyte glycoprotein 35-55-reactive T helper 1 (Th1) and Th17 cells in the periphery and a reduced accumulation of Th1 and Th17 effectors in the central nervous system. We determined that these impaired T cell responses in OGR1-knockout mice associated with a reduced frequency and number of dendritic cells in draining lymph nodes during EAE and a higher production of nitric oxide by macrophages. Our studies suggest that OGR1 plays a key role in regulating T cell responses during autoimmunity.     

Relationship between alpha-helical propensity and formation of the ribonuclease-S complex.

Variant semisynthetic ribonuclease-S complexes were characterized in which the helical glutamic acid 9 residue was replaced by either leucine or glycine. The Leu-9 and Gly-9 synthetic peptides, corresponding otherwise to residues 1 through 15 of bovine pancreatic ribonuclease, were studied with respect to the ability to bind, and generate enzymic activity, with the complementary native protein fragment containing residues 21 through 124 of ribonuclease (RNAase-S-(21–124)). Both the Leu and Gly peptides bind to the RNAase-S-(21–124) to yield complexes with catalytic properties similar to those obtained with the Glu-9-containing peptide of residues 1 through 20 of ribonuclease (RNAase-S-(1–20)). However, whereas the binding affinity of Leu peptide to RNAase-S-(21–124) is only a factor of three less than that for RNAase-S-(1–20), that for Gly peptide is about 20-fold less than that for RNAase-S-(1–20). The stronger binding of Leu than Gly peptide corresponds to the observed propensity of leucine but not glycine for the α-helical conformation in globular proteins.In spite of the weakened affinity of the Gly peptide for RNAase-S-(21–124), it is essentially fully as capable as the Leu-9 and RNAase-S-(1–20) peptides in directing the re-formation of correct disulfide-containing conformation of RNAase-S-(21–124) after disulfide randomization of the latter.