Biology subjects

Shui, Y.

Publications and source records attributed to Shui, Y..

3 recordsLinked to original sources

bioRxiv2026

Programmable De Novo Design of Mesoporous Protein Crystal Frameworks

Three-dimensional protein crystals are ordered, porous macroscopic materials with potential applications in catalysis, biosensing, and biomedicine. However, most protein crystals are obtained by empirical screening, providing limited control over the lattice architecture, pore geometry or component composition that determine material function. Here, we present a modular strategy for the programmable design of highly porous, framework-like protein crystals using predefined protein-protein interactions. This strategy yielded over 30 distinct protein crystals, including single-component and multicomponent P213 and I213 lattices that grow to over 100 micrometers in size. Small-angle X-ray scattering and electron microscopy showed close agreement between experimental lattices and computational models. RFdiffusion-guided design generated isomorphous variants with matched lattice parameters, enabling coherent protein crystal alloys, epitaxial core-shell growth and reversible shell assembly. The designed crystals exhibit tunable mesoporous architectures, with limiting apertures of 2-18 nm, and support genetically encoded incorporation of fluorescent protein guests. These results establish a general route to programmable lattice engineering of protein crystals and position them as genetically encoded, compositionally tunable mesoporous materials.

synthetic biology↗

bioRxiv2025

Melatonin Enhances Sleep via MT1-Driven Activation of Slo1 in Suprachiasmatic Nucleus Neurons

Melatonin promotes sleep through mechanisms that have remained elusive. Here, we identify a molecular pathway by which melatonin promotes sleep by activating BK channels (Slo1) via MT1 receptors in the suprachiasmatic nucleus (SCN), the brains master circadian clock. In melatonin-proficient CBA/CaJ mice, knockout of either MT1 or Slo1 reduces REM and NREM sleep during the rest phase (daytime), accompanied by prolonged action potentials and diminished afterhyperpolarization in SCN neurons. These electrophysiological and behavioral changes are minimal during the active phase (nighttime). Strikingly, Slo1 expression in the SCN peaks during the daytime, contrary to previous reports, but aligning with its sleep-promoting function. Slo1, but not MT1, deletion also triggers spontaneous seizures, highlighting broader functions beyond circadian control. Structural mapping identifies critical domains mediating MT1-Slo1 coupling. Together, these findings position the MT1-Slo1 signaling axis as a core circadian mechanism linking melatonin to sleep regulation and a potential therapeutic target for sleep disorders.

neuroscience↗

bioRxiv2024

One pot RNA:DNA assembly for ribosomal RNA detection of pathogenic bacteria with single-molecule sensitivity

Ribosomal RNAs (rRNAs) serve as species-defining markers and undergo processing steps such as excision of intervening sequences (IVSs). Direct analysis of native rRNAs is hampered by amplification-induced biases and by the high conservation of rRNA sequences, which complicates discrimination of closely related variants. Here, we present modular RNA:DNA nanostructures that enable direct, amplification-free identification of rRNAs and their variants. The approach employs rationally designed RNA:DNA duplexes, named RNA identifiers (IDs), assembled onto native rRNAs via short complementary oligonucleotides bearing programmable coding motifs. We demonstrate that native bacterial 16S rRNAs can be directly converted into RNA IDs and detected with solid-state nanopores. Having established direct rRNA readout, we next show that biologically encoded rRNA processing states, including serovar-specific 23S rRNA fragmentation patterns arising from IVS excision, are resolved using RNA IDs. Finally, to extend discrimination beyond processing-level differences, we incorporate catalytically inactive Cas9 ribonucleoprotein complexes to enable single-nucleotide discrimination of rRNA variants. Our modular RNA ID-nanopore system facilitates studying rRNA processing and rRNA diversity.

biophysics↗