FEBS Letters

Illingworth, Sam

doi: 10.1002/1873-3468.13891pmid: N/A

Science communication is often perceived as an opportunity for scientists to broadcast their expertise and knowledge to a general public, so that this lay audience might better understand a specific field of study. However, in order for science to be made more accessible, science communication initiatives need to move away from this one‐way discourse aimed at an unrealistically homogeneous public. Instead, science communicators need to consider how best to engage multiple audiences in a two‐way communication that can both inform research governance and lead to the cocreation of new knowledge. In this article, I discuss how poetry and tabletop games provide two media through which scientists can engage nonscientists in meaningful dialogue, helping to address a scientist's social responsibility and diversify science in the process.

Bonne Køhler, Julie; Jers, Carsten; Senissar, Mériem; Shi, Lei; Derouiche, Abderahmane; Mijakovic, Ivan

doi: 10.1002/1873-3468.13797pmid: 32337704

Protein phosphorylation regulates a large variety of biological processes in all living cells. In pathogenic bacteria, the study of serine, threonine, and tyrosine (Ser/Thr/Tyr) phosphorylation has shed light on the course of infectious diseases, from adherence to host cells to pathogen virulence, replication, and persistence. Mass spectrometry (MS)‐based phosphoproteomics has provided global maps of Ser/Thr/Tyr phosphosites in bacterial pathogens. Despite recent developments, a quantitative and dynamic view of phosphorylation events that occur during bacterial pathogenesis is currently lacking. Temporal, spatial, and subpopulation resolution of phosphorylation data is required to identify key regulatory nodes underlying bacterial pathogenesis. Herein, we discuss how technological improvements in sample handling, MS instrumentation, data processing, and machine learning should improve bacterial phosphoproteomic datasets and the information extracted from them. Such information is expected to significantly extend the current knowledge of Ser/Thr/Tyr phosphorylation in pathogenic bacteria and should ultimately contribute to the design of novel strategies to combat bacterial infections.

Markaki, Maria; Tavernarakis, Nektarios

doi: 10.1002/1873-3468.13802pmid: 32350855

Ageing is driven by the inexorable and stochastic accumulation of damage in biomolecules vital for proper cellular function. Although this process is fundamentally haphazard and uncontrollable, genetic and extrinsic factors influence senescent decline and ageing. Numerous gene mutations and treatments have been shown to extend the lifespan of organisms ranging from the unicellular Saccharomyces cerevisiae to primates. Most such interventions ultimately interface with cellular stress response mechanisms, suggesting that longevity is intimately related to the ability of the organism to counter both intrinsic stress and extrinsic stress. Mitochondria, the main energy hub of the cell, are highly dynamic organelles, playing essential roles in cell physiology. Mitochondrial function impinges on several signalling pathways modulating cellular metabolism, survival and healthspan. Maintenance of mitochondrial function and energy homeostasis requires both generation of new healthy mitochondria and elimination of the dysfunctional ones. Here, we survey the mechanisms regulating mitochondrial number in cells, with particular emphasis on neurons. We, further, discuss recent findings implicating perturbation of mitochondrial homeostasis in cellular senescence and organismal ageing as well as in age‐associated neurodegenerative diseases.

Alba, Eva

doi: 10.1002/1873-3468.13889pmid: 32735703

Marleaux, Michael; Anand, Kanchan; Latz, Eicke; Geyer, Matthias

doi: 10.1002/1873-3468.13865pmid: 32542665

Inflammasomes are cytosolic multimeric signaling complexes of the innate immune system that induce activation of caspases. The NOD‐like receptor NLRP9 recruits the adaptor protein ASC to form an ASC‐dependent inflammasome to limit rotaviral replication in intestinal epithelial cells, but only little is known about the molecular mechanisms regulating and driving its assembly. Here, we present the crystal structure of the human NLRP9 pyrin domain (PYD). We show that NLRP9PYD is not able to self‐polymerize nor to nucleate ASC specks in HEK293T cells. A comparison with filament‐forming PYDs revealed that NLRP9PYD adopts a conformation compatible with filament formation, but several charge inversions of interfacing residues might cause repulsive effects that prohibit self‐oligomerization. These results propose that inflammasome assembly of NLRP9 might differ largely from what we know of other inflammasomes.

Encarnação, João Crispim; Napolitano, Valeria; Opassi, Giulia; Danielson, U. Helena; Dubin, Grzegorz; Popowicz, Grzegorz M.; Munier‐Lehmann, Hélène; Buijs, Jos; Andersson, Karl; Björkelund, Hanna

doi: 10.1002/1873-3468.13847pmid: 32473599

The interaction between the Shiga toxin B‐subunit (STxB) and its globotriaosylceramide receptor (Gb3) has a high potential for being exploited for targeted cancer therapy. The primary goal of this study was to evaluate the capacity of STxB to carry small molecules and proteins as cargo into cells. For this purpose, an assay was designed to provide real‐time information about the StxB–Gb3 interaction as well as the dynamics and mechanism of the internalization process. The assay revealed the ability to distinguish the process of binding to the cell surface from internalization and presented the importance of receptor and STxB clustering for internalization. The overall setup demonstrated that the binding mechanism is complex, and the concept of affinity is difficult to apply. Hence, time‐resolved methods, providing detailed information about the interaction of STxB with cells, are critical for the optimization of intracellular delivery.

Trempel, Fabian; Eschen‐Lippold, Lennart; Bauer, Nicole; Ranf, Stefanie; Westphal, Lore; Scheel, Dierk; Lee, Justin

doi: 10.1002/1873-3468.13850pmid: 32484235

Changes in cellular calcium levels are one of the earliest signalling events in plants exposed to pathogens or other exogenous factors. In a genetic screen, we identified an Arabidopsis thaliana ‘changed calcium elevation 1’ (cce1) mutant with attenuated calcium response to the bacterial flagellin flg22 peptide and several other elicitors. Whole‐genome resequencing revealed a mutation in asparagine‐linked glycosylation 12 that encodes the mannosyltransferase responsible for adding the eighth mannose residue in an α‐1,6 linkage to the dolichol‐PP‐oligosaccharide N‐glycosylation glycan tree precursors. While properly targeted to the plasma membrane, misglycosylation of several receptors in the cce1 background suggests that N‐glycosylation is required for proper functioning of client proteins.

Wang, Xiang; Gao, Yupeng; Guan, Zeyuan; Xie, Zhaoqi; Zhang, Delin; Yin, Ping; Yang, Guangsheng; Hong, Dengfeng; Xin, Qiang

doi: 10.1002/1873-3468.13817pmid: 32415887

MS5 is a meiosis‐related protein belonging to the Brassicaceae‐specific domain of unknown function family and characterized by the MS5 superfamily domain (MSD). In this study, we elucidated the three‐dimensional crystal structure and potential biochemical function of the MSD. It was observed that the MSD adopts a cystatin‐like fold, mainly consisting of a central α‐helix and four‐ or five‐stranded antiparallel β‐sheets that wrap around it. However, unlike cystatins, which inhibit cysteine proteases, the MSD displayed allosteric activation of papain. We believe that our study provides insight into novel mechanisms of proteolytic enzyme regulation and may serve as a basis for functional studies of the MS5 family proteins in plants.