Biology subjects

Hu, Y.-Y.

Publications and source records attributed to Hu, Y.-Y..

3 recordsLinked to original sources

bioRxiv2024

Mycobacterium tuberculosis CrgA Forms a Dimeric Structure with Its Transmembrane Domain Sandwiched between Cytoplasmic and Periplasmic β-Sheets, Enabling Multiple Interactions with Other Divisome Proteins

CrgA is a key transmembrane (TM) protein in the cell division process of Mycobacterium tuberculosis (Mtb), the pathogen responsible for tuberculosis. While many of the Mtb divisome proteins have been identified, their structures and interactions remain largely unknown. Previous studies of CrgA using oriented-sample solid-state NMR have defined the tilt and rotation of the TM helices, but the cytoplasmic and periplasmic domains and even the oligomeric state were uncharacterized. Here, combining oriented-sample and magic-angle spinning solid-state NMR spectra, we solved the full-length structure of CrgA. The structure features a dimer with a TM domain sandwiched between a cytoplasmic {beta}-sheet and a periplasmic {beta}-sheet. The {beta}-sheets stabilize dimerization, which in turn increases CrgAs ability to participate in multiple protein interactions. Within the membrane, CrgA binds FtsQ, CwsA, PbpA, FtsI, and MmPL3 via its TM helices; in the cytoplasm, Lys23 and Lys25 project outward from the {beta}-sheet to interact with acidic residues of FtsQ and FtsZ. The structural determination of CrgA thus provides significant insights into its roles in recruiting other divisome proteins and stabilizing their complexes for Mtb cell wall synthesis and polar growth.

biophysics↗

bioRxiv2020

G protein-Coupled Receptor Distribution Impacts the Effectiveness of Signal Transmission.

Numbers of activated receptor dictate efficacy of neurotransmitter stimulation. Many PLC coupled receptors activated by ligands elicit canonical downstream Gq/11 pathway to induce endogenous Ca2+ gated chloride channels. The coupling from receptors to effectors was analyzed in Xenopus oocytes expressing genetically modified angiotensin receptor type 1 receptor (AT1R). The latency between ATII binding and Ca2+-induced Cl- current surge was inversely correlated. AT1R activation triggered a chain of chemical reactions, of which the products were playing messengers for subsequent events. Messenger accumulation must rate-limit the agonism. For accurate quantification the speed of ATII triggered the i Cl-. The T-form AT1R-IRK1 fusion exhibits faster induction compared to the M-form. The latency of the recorded none vanished i Cl-, marking the lowest genuine calcium activation, took place at earlier time point by the timer time. The evoked i Cl- however reached similar maximal amplitudes. This kinetic effect raises the possibility to use temporal coding to complement amplitude coding (analogous to FM versus AM radio transmission) for receptor-agonist pairs.

neuroscience↗

bioRxiv2019

EphB6 regulates social behavior through gut microbiota-mediated vitamin B6 metabolism and excitation/inhibition balance of medial prefrontal cortex in mice

Autism spectrum disorder (ASD) is a developmental disorder with no effective pharmacological treatments so far. Gut microbiota has been suggested to contribute to autistic symptoms. However, the key genes and the mechanisms linking gut microbiota and brain dysfunctions in ASD are still unclear. Here, we found deletion of EphB6, an ASD-associated candidate gene, induced dysregulated gut microbiota and autism-like behavior in mice. More importantly, transplanting fecal microbiota from EphB6-deficient mice resulted in disturbed gut microbiota and autism-like behavior in antibiotics-treated C57BL/6J mice. Meanwhile, transplanting fecal microbiota from wild-type mice ameliorated disturbed gut microbiota and autism-like behavior in mice with deletion of EphB6. At the metabolic levels, dysregulated gut microbiota led to vitamin B6 and dopamine defects in EphB6-deficient mice. At the cellular levels, excitation/inhibition (E/I) imbalance in medial prefrontal cortex was induced by gut microbiota-mediated defects of vitamin B6 metabolism in EphB6-deficient mice. Our study uncovers a key role for EphB6 in regulation of social behavior by gut microbiota-mediated vitamin B6 metabolism, dopamine synthesis and E/I balance, suggesting a new strategy for treatment of ASD patients.

neuroscience↗