Biology subjects

Li, J.-Y.

Publications and source records attributed to Li, J.-Y..

4 recordsLinked to original sources

bioRxiv2020

Receptor utilization of angiotensin converting enzyme 2 (ACE2) indicates a narrower host range of SARS-CoV-2 than that of SARS-CoV

Coronavirus pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, SARS-CoV caused SARS pandemic in 2003 and SARS-CoV-2 caused the COVID-19 pandemic recently. Both viruses have been reported to originate from bats. Thus, direct or indirect interspecies transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the interspecies transmission. Angiotensin converting enzyme 2 (ACE2) is the receptor of both SARS-CoV and SARS-CoV-2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell-entry assay to evaluate the receptor-utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS-CoV-2 utilized less ACE2s than SARS-CoV, indicating a narrower host range of SARS-CoV-2. Meanwhile, pangolin CoV, another SARS-related coronavirus highly homologous to SARS-CoV-2 in its genome, yet showed similar ACE2 utilization profile with SARS-CoV rather than SARS-CoV-2. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N-terminal 20th and 42nd amino acids that may determine the different receptor utilization of SARS-CoV, SARS-CoV-2 and pangolin CoV. Our studies promote the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses.

microbiology↗

bioRxiv2020

Mycena genomes resolve the evolution of fungal bioluminescence

Mushroom-forming fungi in the order Agaricales represent an independent origin of bioluminescence in the tree of life, yet the diversity, evolutionary history, and timing of the origin of fungal luciferases remain elusive. We sequenced the genomes and transcriptomes of five bonnet mushroom species (Mycena spp.), a diverse lineage comprising the majority of bioluminescent fungi. Two species with haploid genome assemblies [~]150Mb are amongst the largest in Agaricales, and we found that a variety of repeats between Mycena species were differentially mediated by DNA methylation. We show that bioluminescence evolved in the last common ancestor of mycenoid and the marasmioid clade of Agaricales and was maintained through at least 160 million years of evolution. Analyses of synteny across genomes of bioluminescent species resolved how the luciferase cluster was derived by duplication and translocation, frequently rearranged and lost in most Mycena species, but conserved in the Armillaria lineage. Luciferase cluster members were co-expressed across developmental stages, with highest expression in fruiting body caps and stipes, suggesting fruiting-related adaptive functions. Our results contribute to understanding a de novo origin of bioluminescence and the corresponding gene cluster in a diverse group of enigmatic fungal species. SignificanceWe present the genomes of five new bonnet mushroom Mycena species, formerly the last fungal bioluminescent lineage lacking reference genomes. These genome-scale datasets allowed us to construct an evolutionary model pinpointing all possible changes in the luciferase cluster across all fungi and additional genes involved in bioluminescence. We show that luciferase clusters were differentially lost in different fungal lineages and in particular a substantial loss was observed in the Mycena lineage. This can be attributed to genome regions of Mycena underwent different evolutionary dynamics. Our findings offer insights into the evolution of how a gene cluster that emerged 160 million years ago and was frequently lost or maintained due to differences in genome plasticity.

genomics↗

bioRxiv2020

Low-protein/high-carbohydrate diet induces AMPK-dependent canonical and non-canonical thermogenic response in subcutaneous adipose tissue

Low-protein/high-carbohydrate (LPHC) diet promotes metabolic health and longevity in adult humans and animal models. However, the complex molecular underpinnings of how LPHC diet leads to metabolic benefits remain elusive. Through a multi-layered approach, here we observed that LPHC diet promotes an energy-dissipating response consisting in the parallel recruitment of canonical and non-canonical (muscular) thermogenic systems in subcutaneous white adipose tissue (sWAT). In particular, we measured Ucp1 induction in association with up-regulation of actomyosin components and several Serca (Serca1, Serca2a, Serca2b) ATPases. In beige adipocytes, we observed that AMPK activation is responsible for transducing the amino acid lowering in an enhanced fat catabolism, which sustains both Ucp1- and Serca-dependent energy dissipation. Limiting AMPK activation counteracts the expression of brown fat and muscular genes, including Ucp1 and Serca, as well as mitochondrial oxidative genes. We observed that mitochondrial reactive oxygen species are the upstream molecules controlling AMPK-mediated metabolic rewiring in amino acid-restricted beige adipocytes. Our findings delineate a novel metabolic phenotype of responses to amino acid shortage, which recapitulates some of the benefits of cool temperature in sWAT. In conclusion, this highlights LPHC diet as a valuable and practicable strategy to prevent metabolic diseases through the enhancement of mitochondrial oxidative metabolism and the recruitment of different energy dissipating routes in beige adipocytes.

physiology↗

bioRxiv2019

Integrative model to coordinate the oligomerization and aggregation mechanisms of CCL5

The CC-type chemokine ligand 5 (CCL5) is involved in the pathogenesis of many inflammatory conditions. The oligomerization and aggregation of CCL5 are considered to be responsible for its inflammatory properties. The CC-type dimer acts as the basic unit to constitute the oligomer. However, the structural basis of CCL5 oligomerization remains controversial. In this study, NMR and biophysical analyses proposed evidence that no single dimer-dimer interaction dominates in the oligomerization process of CCL5. CCL5 could oligomerize alternatively through two different interactions, E66-K25 and E66-R44/K45. In addition, a newly determined trimer structure reported an interfacial interaction through the N-terminal 12FAY14 sequence. The interaction contributes to aggregation and precipitation. In accordance with the observations, an integrative model explains the CCL5 oligomerization and aggregation process. CCL5 assembly consists of two types of dimer-dimer interactions and one aggregation mechanism. For full-length CCL5, the molecular accumulation triggers oligomerization through the E66-K25 interaction, and the 12FAY14 interaction acts as a secondary effect to derive aggregation. The E66-R44/K45 interaction dominates in CCL5 N-terminal truncations. The interaction would lead to filament-like formation in solution.

biochemistry↗