Stier, L. | Search bioRxiv

bioRxiv2025

Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1

Cellular responses to amino acid fluctuations often hinge on ubiquitin-mediated control of metabolic enzymes, yet the underlying E3 ligase pathways remain incompletely defined. Using quantitative proteomics and active cullin-RING ligase (CRL) profiling, we identify LRRC58 as a cysteine-responsive substrate receptor whose stability increases sharply under cysteine starvation. Proteomics reveals an inverse relationship between LRRC58 and the metabolic enzyme cysteine dioxygenase 1 (CDO1), suggesting a cysteine-linked regulatory axis. Biochemical reconstitution and cryo-EM structures show that LRRC58 forms an active CUL2-or CUL5-based CRL that selectively positions CDO1 for ubiquitylation at Lys8. By contrast, targeted protein degradation via the VHL-based CRL is achieved by recruitment of a distinct surface of CDO1, and more promiscuous ubiquitylation independent of Lys8. Together, our proteomics-guided discovery pipeline, cellular stability studies, and structural analyses uncover a metabolically-tuned LRRC58-CDO1 pathway that links cysteine availability to selective proteasomal turnover, reveals principles of metabolite-regulated CRL activity, and showcases mechanisms distinguishing endogenous and targeted protein degradation.

biochemistry↗

bioRxiv2020

Criteria for effective fallow field eco schemes for farmland birds during non-breeding

O_LIFarmland eco schemes implemented under the current Common Agricultural Policy (CAP) of the European Union are often considered ineffective in halting farmland bird declines. Fallow fields, often seeded with dedicated seed mixtures, rate among the more beneficial eco scheme types. Yet, the CAP currently defines no minimum criteria for fallow fields to qualify as eco scheme, likely jeopardizing their potential biodiversity benefits. C_LIO_LIWe investigated the attractiveness of four fallow field types established under CAP eco schemes and dedicated bird conservation programs in Southern Germany. Our 2-year surveys on > 100 fields focused on the non-breeding season, where food limitation can become particularly problematic. We modelled bird incidences also in response to vegetation structure and adjacent landscape features to derive minimum criteria for effective fallow field eco schemes. C_LIO_LIFallow field types varied only mildly in overall species richness but showed striking differences in the attracted species. Finches in particular tended to preferentially visit 1-year fallow fields, while buntings tended towards 2-year and older field types. 1-year CAP fallows, however, are typically removed before mid-winter, and thus potentially act as a trap to farmland birds and other wildlife. C_LIO_LIThe investigated species consistently preferred larger fallow fields with a more differentiated vegetation structure. Placement close to woods and hedgerows positively affected birds inhabiting woodland ecotones, while classic farmland species showed higher incidences on fallow fields embedded in open landscapes. C_LIO_LI Policy implications Our findings call for the ongoing CAP revisions to specify minimum requirements that qualify fallow fields as eco schemes. These should include an at least biennial cycle, a diversification of seed mixtures, standards for fallow field size, and criteria for their placement in the landscape matrix. C_LI

ecology↗