Showing papers in "Journal of Biological Chemistry in 2020"

TL;DR: The results collectively provide a unifying, refined mechanism of RDV-mediated RNA synthesis inhibition in coronaviruses and define this nucleotide analogue as a direct-acting antiviral.

TL;DR: The selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogs, which may explain the high potency of RDV against RNA viruses in cell-based assays.

TL;DR: The molecular virology of coronavirus infection, including its entry into cells, its remarkably sophisticated gene expression and replication mechanisms, its extensive remodeling of the intracellular environment, and its multifaceted immune evasion strategies are presented.

TL;DR: Recently discovered roles of adhesion molecules in collective cancer cell migration are highlighted and the utility of three-dimensional models in studying cell-cell adhesion is discussed, as well as recent therapeutic approaches targetingadhesion molecules.

TL;DR: The vast array of herbicide-resistance mechanisms for generalist (NTSR) and specialist (TSR and some NTSR) adaptations that have evolved over a few decades illustrate the evolutionary resilience of weed populations to extreme selection pressures.

TL;DR: Although this canonical pathway is the predominant signaling cascade, alternative pathways also affect ethylene responses, and this review summarizes the current understanding of ethylene signaling, including these alternative pathways, and discusses how Ethylene signaling has been manipulated for agricultural and horticultural applications.

TL;DR: It is concluded that SARS–CoV-2 is sensitive to exogenously added IFNs, suggesting that type I and especially the less adverse effect–prone type III IFN are good candidates for the management of COVID-19.

TL;DR: Evidence suggesting that these repeats are a payoff for the advantages of having abundant simple-sequence repeats for eukaryotic genome function and evolvability is described.

TL;DR: Structural and functional analyses revealed that both elements promote similar −1 PRF rates and that silent coding mutations in the slippery sites and in all three stems of the pseudoknot strongly ablate −1PRF activity.

TL;DR: The current understanding of tetrapyrrole biogenesis represents a remarkable biochemical milestone that is summarized in this review.

TL;DR: Gaps in understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity are identified and changes in the brain leading to physiological effects throughout the body and vice versa are identified.

TL;DR: The findings show that inflammatory cell death, PANoptosis, is induced by coronavirus infection and that impaired NLRP3 inflammasome function or pyroptosis can lead to negative consequences for the host.

TL;DR: This review aims to outline the major roles of physiological and pathological hypoxic conditions in the maintenance of intestinal homeostasis and in the onset and progression of disease with a major focus on understanding the complex pathophysiology of the intestine.

TL;DR: This review focuses on recent progress of different strategies, including protein engineering, redox-partner engineering, substrate engineering, electron source engineering, and P450-mediated metabolic engineering, in efforts to more efficiently produce pharmaceuticals and other chemicals.

TL;DR: The collective data provide strong evidence to show that template-dependent inhibition of SARS–CoV-2 RdRp by RDV is biologically relevant.

TL;DR: It is proposed that BACH1 controls the threshold of ferroPTosis induction and may represent a therapeutic target for alleviating ferroptosis-related diseases, including myocardial infarction.

TL;DR: The results show that mTORC1 is differentially regulated by amino acids through two distinct pathways, including the Rag-dependent and Rag-independent pathways, and that eight amino acids filter through the Rag GTPase pathway.

TL;DR: The data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

TL;DR: The ultimate challenge is to decipher the comprehensive and combinatorial array of PTMs that modulate Hsp90 chaperone function, a phenomenon termed the “chaperone code.”

TL;DR: Cumulatively, it is evident that truncation of αsyn, particularly carboxyl truncation that can be augmented by dysfunctional proteostasis, dramatically potentiates the propensity ofαsyn to pathologically misfold into uniquely toxic fibrils with modulated prion-like seeding activity.

TL;DR: The room-temperature neutron structure of 3CL Mpro was presented, which allowed direct determination of hydrogen atom positions and, hence, protonation states in the protease, and observed that the catalytic site natively adopts a zwitterionic reactive form.

TL;DR: A detailed layout of the current theorized modes of AGPCR activation is provided with discussion of potential parallels to mechanisms used by other GPCR classes and a classification means for the ligands that have been identified and how these ligands may activate AGPCRs in physiological contexts is provided.

TL;DR: The history of the Hsp70 chaperones, its currently understood regulation and functions, and thoughts on what the future of research into the chaperone code may entail are discussed.

TL;DR: The essential role of the Z α2 domain of ZBP1 is identified in several physiological functions and a link between Z-RNA sensing via the Zα2 domain and promotion of influenza-induced PANoptosis and perinatal lethality is established.

TL;DR: It is shown that an ATP-dependent human chaperone system disassembles Tau fibrils in vitro, and it is concluded that the activity of the Hsp70 disaggregation machinery is a double-edged sword, as it eliminates Tau amyloids at the cost of generating new seeds.

TL;DR: Future studies will need to address technical challenges such as how to accurately measure individual tissue thermogenesis in humans; how to safely activate BAT and other organ thermogenesis; and how to sustain a negative energy balance over many years of treatment.

TL;DR: The results demonstrate that C. albicans and A. fumigatus infection induced inflammatory programmed cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis) and that ZBP1 plays a vital role in inflammasome activation and PANoptosis in response to fungal pathogens.

TL;DR: Practical aspects of studying LLPS by NMR are discussed, recent work on the molecular aspects of LLPS of various protein systems are summarized, and future opportunities for characterizing the molecular details ofLLPS to modulate phase separation are discussed.

TL;DR: In this paper, the authors investigated the effect of SARS-CoV-2 spike protein on the enzymatic activity of ACE2 and found that it increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog.

TL;DR: A new dimension is brought to understanding the relationship between zinc homeostasis and the pathogenic process in AD and related neurodegenerative disorders by showing that the divalent transition metal zinc strongly promotes this process, shifting the equilibrium phase boundary to lower protein or crowding agent concentrations.