Biology subjects

Nielsen, O.

Publications and source records attributed to Nielsen, O..

3 recordsLinked to original sources

bioRxiv2026

Structural homology reveals cerato-platanins as conserved antimicrobials repeatedly co-opted for fungal host colonization

Fungal cerato-platanins (CPs) are small ([~]12 kDa) secreted proteins broadly conserved across filamentous fungi and implicated in a striking diversity of biological processes, ranging from fungal development to interactions with plant hosts. However, a core molecular activity unifying these diverse functions has remained elusive. Fungal pathogens secrete effector proteins, including CPs, to manipulate host physiology and promote colonization. Increasing evidence demonstrates that particular fungal effectors possess antimicrobial activity that enables pathogens to reshape host-associated microbiota during infection, and that antimicrobial activity is strongly enriched among evolutionarily conserved secreted proteins. These findings suggests that intermicrobial competition represents an ancient and fundamental fungal trait, and that several effectors that manipulate plant hosts evolved from ancient antimicrobials. Here, we identify antimicrobial activity as the conserved core function of the CP family, from which diverse roles in environmental adaptation and host interaction evolved. Structural analysis of the Verticillium dahliae secretome identified a structural cluster containing the CP protein CP1 and the previously characterized antimicrobial effector Ave1, providing the first structural link between CPs and antimicrobial activity. Accordingly, functional assays demonstrate that V. dahliae CPs exhibit selective antimicrobial activity in vitro. Expanding this analysis to a wide diversity of phylogenetic lineages and ecological lifestyles revealed that antimicrobial features are broadly conserved across the CP family. Together, our findings identify antimicrobial activity as an ancient and conserved molecular function that unifies the CP family and support a model in which host-manipulating effector functions evolved from ancestral proteins that mediate inter-microbial competition.

microbiology↗

bioRxiv2023

Checkpoint activation by Spd1: a competition-based system relying on tandem disordered PCNA binding motifs

DNA regulation, replication and repair are processes fundamental to all known organisms and the sliding clamp proliferating cell nuclear antigen (PCNA) is central to all these processes. S-phase delaying protein 1 (Spd1) from S. pombe, an intrinsically disordered protein that causes checkpoint activation by inhibiting the enzyme ribonucleotide reductase, has one of the most divergent PCNA binding motifs known. Using NMR spectroscopy, in vivo assays, X-ray crystallography, calorimetry, and Monte Carlo simulations, an additional PCNA binding motif in Spd1, a PIP-box, is revealed. The two tandemly positioned, low affinity sites exchange rapidly on PCNA exploiting the same binding sites. Increasing or decreasing the binding affinity between Spd1 and PCNA through mutations of either motif compromised the ability of Spd1 to cause checkpoint activation in yeast. These results pinpoint a role for PCNA in Spd1-mediated checkpoint activation and suggest that its tandemly positioned short linear motifs create a neatly balanced competition-based system, involving PCNA, Spd1 and the small ribonucleotide reductase subunit, Suc22R2. Similar mechanisms may be relevant in other PCNA binding ligands where divergent binding motifs so far have gone under the PIP-box radar.

biophysics↗

bioRxiv2018

Comprehensive profiling of the fission yeast transcription start site activity during stress and media response

Fission yeast, Schizosaccharomyces pombe, is an attractive model organism for transcriptional and chromatin biology research. Such research is contingent on accurate annotation of transcription start sites (TSSs). However, comprehensive genome-wide maps of TSSs and their usage across commonly applied laboratory conditions and treatments for S. pombe are lacking. To this end, we profiled TSS activity genome-wide in S. pombe cultures exposed to heat shock, nitrogen starvation, hydrogen peroxide and two commonly applied media, YES and EMM2, using Cap Analysis of Gene Expression (CAGE). CAGE-based annotation of TSSs is substantially more accurate than existing PomBase annotation; on average, CAGE TSSs fall 50-75 bp downstream of PomBase TSSs and co-localize with nucleosome boundaries. In contrast to higher eukaryotes, S. pombe does not show sharp and dispersed TSS distributions. Our data recapitulate known S. pombe stress expression response patterns and identify stress- and mediaresponsive alternative TSSs. Notably, alteration of growth medium induces changes of similar magnitude as some stressors. We show a link between nucleosome occupancy and genetic variation, and that the proximal promoter region is genetically diverse between S. pombe strains. Our detailed TSS map constitute a central resource for S. pombe gene regulation research.

genomics↗