High-affinity neurotrophin-3 (NT3) receptors have been identified on nerve growth factor (NGF)-dependent sympathetic neurons, but their occupancy by NT3 does not lead to neuronal survival. The molecular nature of these NT3 binding sites was investigated in this study. With freshly dissociated embryonic day 11 (E11) chick sympathetic neurons, cross-linking experiments revealed that the main rece...

The neurotrophin receptor p75(NTR) conveys multiple signals via its intracellular death domain. However, how the death domain is activated and interacts with downstream adaptors remains unclear. Here, we report two crystal structures of the p75(NTR) death domain in the form of a non-covalent asymmetric dimer and a Cys379-Cys379 disulfide bond linked symmetric dimer, respectively. These two dime...

Interferon-induced ISG15 conjugation plays an important antiviral role against several viruses, including influenza viruses. The NS1 protein of influenza B virus (NS1B) specifically binds only human and nonhuman primate ISG15s and inhibits their conjugation. To elucidate the structural basis for the sequence-specific recognition of human ISG15, we determined the crystal structure of the complex...

OBJECTIVES The objective of this study was to identify the mechanisms of resistance to nifurtimox and fexinidazole in African trypanosomes. METHODS Bloodstream-form Trypanosoma brucei were selected for resistance to nifurtimox and fexinidazole by stepwise exposure to increasing drug concentrations. Clones were subjected to WGS to identify putative resistance genes. Transgenic parasites modula...

Chimeric poliovirus RNAs, possessing the 5' nontranslated region (NTR) of hepatitis C virus in place of the 5' NTR of poliovirus, were used to examine the role of the poliovirus 5' NTR in viral replication. The chimeric viral RNAs were incubated in cell-free reaction mixtures capable of supporting the sequential translation and replication of poliovirus RNA. Using preinitiation RNA replication ...

The p75 neurotrophin receptor (p75(NTR)) is expressed by neurons particularly vulnerable in Alzheimer's disease (AD). We tested the hypothesis that non-peptide, small molecule p75(NTR) ligands found to promote survival signaling might prevent Abeta-induced degeneration and synaptic dysfunction. These ligands inhibited Abeta-induced neuritic dystrophy, death of cultured neurons and Abeta-induced...

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UNLABELLED Two branches of the phosphoenolpyruvate-phosphotransferase system (PTS) operate in the soil bacterium Pseudomonas putida KT2440. One branch encompasses a complete set of enzymes for fructose intake (PTS(Fru)), while the other (N-related PTS, or PTS(Ntr)) controls various cellular functions unrelated to the transport of carbohydrates. The potential of these two systems for regulating ...

Neurotrophins promote neuronal survival and differentiation by binding to two classes of cell surface receptors: members of the Trk-family receptor tyrosine kinases and p75(NTR), a member of the tumor necrosis factor receptor superfamily. The discoveries that the unprocessed proneurotrophin peptide is both a preferential high-affinity ligand for p75(NTR) (with minimal affinity for trkA) and a p...