No abstract

High-resolution membrane protein structures are essential for a fundamental understanding of the molecular basis of diverse cellular processes and for drug discovery. Detergents are widely used to extract membrane-spanning proteins from membranes and maintain them in a functional state for downstream characterization. Due to limited long-term stability of membrane proteins encapsulated in conventional detergents, development of novel agents is required to facilitate membrane protein structural study. In the current study, we designed and synthesized tris(hydroxymethyl)aminomethane linker-bearing triazine-based triglucosides (TTGs) for solubilization and stabilization of membrane proteins. When these glucoside detergents were evaluated for four membrane proteins including two G protein-coupled receptors, a few TTGs including TTG-C10 and TTG-C11 displayed markedly enhanced behaviors toward membrane protein stability relative to two maltoside detergents [DDM (n-dodecyl-β-d-maltoside) and LMNG (lauryl maltose neopentyl glycol)]. This is a notable feature of the TTGs as glucoside detergents tend to be inferior to maltoside detergents at stabilizing membrane proteins. The favorable behavior of the TTGs for membrane protein stability is likely due to the high hydrophobicity of the lipophilic groups, an optimal range of hydrophilic–lipophilic balance, and the absence of cis–trans isomerism.

Although there has been enormous progress in the last half-century in the drug discovery targeting obesity and associated co-morbidities, the clinical treatment of obesity remains tremendously challenging. GPR75 is an orphan receptor and is suggested to be a potential novel target for the control of obesity and related metabolic disorders. Inhibition of the GPR75 signaling pathway by small molecules, antibodies, or genetic manipulations may provide a therapeutic strategy for obesity. Here, we report the active-like Cryo-EM structure of human GPR75 with an intracellular nanobody, which reveals the receptor activation mechanism. The extensive interaction network required to achieve the active structure helps explain the allosteric coupling between the orthosteric pocket and the G-protein coupling domain. The well-defined orthosteric ligand binding pocket of human GPR75 provides a structural basis for anti-obesity drug discovery.

Messenger RNAs exchanged between scions and rootstocks of grafted plants seriously affect their traits performance. The study goals were to identify the long-distance mRNA transmission events in grafted willows using a transcriptome analysis and to reveal the possible effects on rooting traits. The results showed that the Salix matsudana variety 9901 has better rooting ability than YJ, which reasonably improved the rooting performance of the heterologous grafts 9901 (scion) / YJ (rootstock). A transcriptome analysis showed that 2,948 differentially expressed genes (DEGs) were present in the rootstock of 9901/YJ grafted plants in comparison with YJ/YJ. Among them, 692 were identified as mRNAs moved from 9901 scion based on a SNP analysis of two parents. They were mostly 1,001–1,500 bp, had 40–45% GC contents, or had expression abundance values less than 10. However, mRNAs over 4,001 bp, having 50–55% GC contents, or having expression abundance values of 10–20 were preferentially transferred. Eight mRNAs subjected to long-distance trafficking were involved in the plant hormone pathways and may significantly promote the root growth of grafted plants. Thus, heterologous grafts of Salix matsudana could efficiently influence plant rooting since of the mRNAs transport from scion to rootstock. Thus, the grafting parents and grafting patterns would be much concerned in the breeding process to gain the expected results in future.