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Erlandson, S.

Publications and source records attributed to Erlandson, S..

4 recordsLinked to original sources

Divergent activation of the RXFP1 relaxin receptor by protein and small molecule agonists

RXFP1 is an unusual G protein-coupled receptor (GPCR) that mediates physiological adaptations to pregnancy and is a therapeutic target due to its benefits in treatment of fibrosis and heart failure. Protein and small-molecule agonists are currently in mid-stage clinical trials. Here, we present three cryo-electron microscopy structures of RXFP1: ligand-free, bound to the native agonist relaxin-2, and bound to the small-molecule drug candidate AZD5462. These structures show that relaxin-2 engages the receptors ectodomain while AZD5462 binds within transmembrane domain. Together with hydrogen-deuterium exchange mass spectrometry, we show that relaxin-2 induces conformational reorganization of the linker domain into a helical secondary structure. In contrast, AZD5462 stabilizes a unique active conformation capable of inducing {beta}-arrestin recruitment. Both mechanisms are distinctive from the "push-pull" mechanism of glycoprotein hormone receptors. Altogether, our findings define divergent activation mechanisms for protein and small-molecule agonists of RXFP1 and provide structural framework for next-generation drug discovery targeting relaxin receptors and their relatives.

biochemistry↗

Fungal communities from geothermal soils in Yellowstone National Park

Geothermal soils offer unique insight into the way extreme environmental factors shape communities of organisms. However, little is known about the fungi growing in these environments and in particular how localized steep abiotic gradients affect fungal diversity. We used metabarcoding to characterize soil fungi surrounding a hot spring-fed thermal creek with water up to 84 {degrees}C and pH 10 in Yellowstone National Park. We found a significant association between fungal communities and soil variable principal components, and we identify the key trends in co-varying soil variables that explain the variation in fungal community. Saprotrophic and ectomycorrhizal fungi community profiles followed, and were significantly associated with, different soil variable principal components, highlighting potential differences in the factors that structure these different fungal trophic guilds. In addition, in vitro growth experiments in four target fungal species revealed a wide range of tolerances to pH levels but not to heat. Overall, our results documenting turnover in fungal species within a few hundred meters suggest many co-varying environmental factors structure the diverse fungal communities found in the soils of Yellowstone National Park.

ecology↗

Evidence for microbiome-dependent chilling tolerance in Sorghum

Early season chilling stress is a major constraint on sorghum production in temperate climates. Chilling-tolerant sorghum is an active area of development, but the potential for early season microbial-enhanced chilling tolerance in sorghum has not yet been explored. In this study, we characterized traits of field-grown sorghum accessions in response to chilling and non-chilling temperatures and the corresponding cohorts of phyllosphere fungal and bacterial taxa. Further, we characterized the effects of chilling temperatures and microbial inoculation on sorghum accession traits in a growth chamber experiment. By comparing sorghum trait responses under chilling stress with and without soil microbial inoculation, we were able to detect a potential microbe-dependent sorghum response to chilling stress. Four sorghum genotypes showed a negative response to chilling stress with vs. without microbial inoculation, while five sorghum accessions show increased shoot biomass or leaf area under chilling stress when inoculated with a soil microbiome. These differential responses provides opportunities to exploit beneficial microbial taxa for enhancing early-stage chilling tolerance in sorghum, with a potential to be extended to other crops.

plant biology↗

Partitioning plant genetic and environmental drivers of above and belowground community assembly

Host-plant genetic variation affects the diversity and composition of associated above and belowground communities. Most evidence supporting this view is derived from studies within a single common garden, thereby constraining the range of biotic and abiotic environmental conditions that might directly or indirectly (via phenotypic plasticity) affect communities. If natural variability in the environment renders host-plant genetic effects on associated communities unimportant, then studying the community-level consequences of genetic variation may not be warranted. We addressed this knowledge gap by planting a series of common gardens consisting of 10 different clones (genotypes) of the willow Salix hookeriana in a coastal dune ecosystem and manipulated natural variation in ant-aphid interactions (biotic) and wind exposure (abiotic) in two separate experiments. We then quantified the responses of associated species assemblages both above (foliar arthropods) and belowground (rhizosphere fungi and bacteria). In addition, we quantified plant phenotypic responses (plant growth, leaf quality, and root quality) to tease apart the effects of genetic variation, phenotypic plasticity, and direct environmental effects on associated communities. In the ant-aphid experiment, we found that willow genotype explained more variation in foliar arthropod communities than aphid additions and proximity to aphid-tending ant mounds. However, aphid additions modified willow genetic effects on arthropod community composition by attracting other aphid species to certain willow genotypes. In the wind experiment, wind exposure explained more variation than willow genotype in structuring communities of foliar arthropods and rhizosphere bacteria. Still, willow genotype had strong effect sizes on several community properties of arthropods and fungi, indicating that host-plant genetic variation remains important. Across both experiments, genetic variation in plant traits was more important than phenotypic plasticity in structuring associated communities. The relative importance of genetic variation vs. direct environmental effects though depended on the type of environmental gradient (G > E-aphid, but E-wind > G). Taken together, our results suggest that host-plant genetic variation is an important driver of above and belowground biodiversity, despite natural variation in the biotic and abiotic environment.

ecology↗