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MIAO, Y.

Publications and source records attributed to MIAO, Y..

3 recordsLinked to original sources

From Pan-Life Phase Insights to PhaseHub: Analyzing Condensate Complexity

Macromolecular condensation is crucial in biological signaling pathways that regulate development and adaptation processes. However, lacking conserved residues in disordered region of condensate proteins hampers alignment-based analyses of their evolutionary trajectory. To gain a comprehensive overview of phase-separating protein evolution across the Tree of Life, we analyzed phase-separating proteins of proteomes from 1,106 species. Eukaryotes and prokaryotes showed high contrast in need for phase-separating proteins and with a clear genome size-dependent correlation. Evolutionary success appears to hinge on the balance between functional condensation and avoiding harmful aggregation-prone biophysical signatures, such as certain amino acid homorepeats embedded in molecular grammar. We also identified potential phase separation-regulated signaling hubs across kingdoms by integrating phase-separation-positive proteins with protein abundance and interactome data across four model eukaryotic species. Consequently, we created PhaseHub (https://phasehub.sbs.ntu.edu.sg/), a user-friendly interface that explores key scaffold proteins and binders to pinpoint associated partners and potential multicomponent phase separation hubs. TeaserAnalyse phase separation behavior of 1,106 species across kingdoms on proteome level reconstruct the evolutional history of protein condensation.

systems biology↗

Membrane curvature catalyzes actin nucleation through nano-scale condensation of N-WASP-FBP17

Actin remodeling is spatiotemporally regulated by surface topographical cues on the membrane for signaling across diverse biological processes. Yet, the mechanism dynamic membrane curvature prompts quick actin cytoskeletal changes in signaling remain elusive. Leveraging the precision of nanolithography to control membrane curvature, we reconstructed catalytic reactions from the detection of nano-scale curvature by sensing molecules to the initiation of actin polymerization, which is challenging to study quantitatively in living cells. We show that this process occurs via topographical signal-triggered condensation and activation of the actin nucleation-promoting factor (NPF), Neuronal Wiskott-Aldrich Syndrome protein (N-WASP), which is orchestrated by curvature-sensing BAR-domain protein FBP17. Such N-WASP activation is fine-tuned by optimizing FBP17 to N-WASP stoichiometry over different curvature radii, allowing a curvature-guided macromolecular assembly pattern for polymerizing actin network locally. Our findings shed light on the intricate relationship between changes in curvature and actin remodeling via spatiotemporal regulation of NPF/BAR complex condensation.

molecular biology↗

The bacterial quorum sensing signal DSF hijacks Arabidopsis thaliana sterol biosynthesis to suppress plant innate immunity

Quorum sensing (QS) is a recognized phenomenon that is crucial for regulating population-related behaviors in bacteria. However, the direct specific effect of QS molecules on host biology is largely under-studied. In this work, we show that the QS molecule DSF (cis-11-methyl-dodecenoic acid) produced by Xanthomonas campestris pv. campestris can suppress pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) in Arabidopsis thaliana, mediated by flagellin-induced activation of flagellin receptor FLS2. The DSF-mediated attenuation of innate immunity results from the alteration of oligomerization states and endocytic internalization of plasma membrane FLS2. DSF altered the lipid profile of Arabidopsis, with a particular increase of the phytosterol species, which impairs the general endocytosis pathway mediated by clathrin and FLS2 nano-clustering on the plasma membrane. The DSF effect on receptor dynamics and host immune responses could be entirely reversed by sterol removal. Together, our results highlighted the importance of sterol homeostasis to plasma membrane organization and demonstrate a novel mechanism by which pathogenic bacteria use their communicating molecule to manipulate PAMP-triggered host immunity. SIGNIFICANCE STATEMENTBacteria rely on small signalling molecules called quorum sensing (QS) signals to communicate and coordinate their behaviors. QS is known to regulate gene expression, production of virulence factors, and biofilm formation for pathogenic bacteria to effectively colonize their hosts and cause diseases. In this work, we found a class of QS molecule called diffusible-signal factor (DSF), produced by devastating phytopathogenic bacteria such as Xanthomonas spp. and Xylella fastidiosa, could communicate directly with plant host and subvert plant innate immunity by inducing plant sterol production and thereby, attenuating receptor signalling through hindering the receptor clustering and plant endocytosis. The results significantly enrich our understanding of the mechanisms in the tug-of-war between bacterial pathogenesis and host immunity.

plant biology↗