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Shira Weingarten-Gabbay Susan Klaeger Siranush Sarkizova Leah R. Pearlman Da-Yuan Chen Kathleen M.E. Gallagher Matthew R. Bauer Hannah B. Taylor W. Augustine Dunn Christina Tarr John Sidney Suzanna Rachimi Hasahn L. Conway Katelin Katsis Yuntong Wang Del Leistritz-Edwards Melissa R. Durkin Christopher H. Tomkins-Tinch Pardis C. Sabeti 《Cell》2021,184(15):3962-3980.e17
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Minor nucleotides in tRNA from blue-green algae [proceedings 总被引:1,自引:0,他引:1
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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. 相似文献
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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. 相似文献
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