Biology subjects

xu, p.

Publications and source records attributed to xu, p..

3 recordsLinked to original sources

bioRxiv2025

HPV16 E2 protein possesses intrinsic helicase activity and sterically hinders E1 function through direct interaction

HPV16 E2 protein is a key regulatory protein essential for viral replication, yet no enzymatic activity had been attributed to it until now. In this study, we report for the first time that E2 possesses intrinsic ATP-dependent DNA unwinding activity. Mutational analysis identified residues K299, Y303, and K306 as critical for this helicase function. We further demonstrate that podophyllotoxin directly binds to E2 and inhibits its unwinding activity with an IC50 of 0.1074 {micro}M, mediated primarily by residues Q320 and H342. Comparative analysis revealed that the ATPase and helicase activities of E2 are considerably weaker than those of E1. Notably, we discovered that E2 potently inhibits the helicase activity of E1. This suppression is facilitated by the N-terminal domain of E2 (amino acids 1-245) through direct interaction with E1, with residue E39 playing a critical role. Our findings not only unveil a previously unrecognized enzymatic function of E2 but also suggest its role as a potential antiviral target. Moreover, the observed inhibitory effect of E2 on E1 highlights a novel regulatory mechanism for HPV DNA replication. Synopsis O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/676238v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@12fd0aforg.highwire.dtl.DTLVardef@2dc50forg.highwire.dtl.DTLVardef@e46f5eorg.highwire.dtl.DTLVardef@14b87da_HPS_FORMAT_FIGEXP M_FIG C_FIG E2 protein has traditionally been recognized primarily for its DNA-binding and transcriptional regulatory functions. This study provides the first evidence that E2 protein possesses intrinsic enzymatic activity, identifies a small-molecule inhibitor targeting this activity, and reveals a novel mechanism of E1-E2 interaction. O_LIHPV16 E2 Protein Exhibits ATPase and Helicase Activities C_LIO_LIIdentification of Key Amino Acid Residues for HPV16 E2 Protein Enzymatic Activity C_LIO_LIPPT Effectively Inhibits E2 Protein Helicase Activity In Vitro C_LIO_LIE2 Protein Exhibits Weaker Enzymatic Activity Than E1 and Inhibits E1 Helicase Activity C_LIO_LIE2 Inhibits E1 Helicase Activity Through Protein-Protein Interaction C_LI

molecular biology↗

bioRxiv2023

A glutamatergic DRN-VTA pathway for neuropathic pain and comorbid depression-like behavior modulation

Chronic pain causes both physical suffering and comorbid mental disorders such as depression. However, the neural circuits and molecular mechanisms underlying these maladaptive behaviors remain elusive. Here, we report a pathway from vesicular glutamate transporter3 neurons in the dorsal raphe nucleus to dopamine neurons in the ventral tegmental area (VGluT3DRN[->]DAVTA), of which population activity in response to innocuous mechanical stimuli and sucrose consumption, is respectively inhibited and attenuated by chronic neuropathic pain. Mechanistically, neuropathic pain dampens VGluT3DRN[->]DAVTA glutamatergic transmission and DAVTA neural excitability. VGluT3DRN[->]DAVTA activation alleviates neuropathic pain and comorbid depression-like behavior (CDB) by releasing glutamate, which subsequently promotes DA release in the nucleus accumbens medial shell (NAcMed) and produces analgesia and antidepressant effects via D2 and D1 receptors, respectively. In addition, VGluT3DRN[->]DAVTA inhibition produces pain-like hypersensitivity and depression-like behavior in healthy mice. These findings reveal a novel VGluT3DRN[->]DAVTA[->]D2/D1NAcMed pathway in establishing and modulating chronic pain and comorbid depressive-like behavior.

neuroscience↗

bioRxiv2019

Transcriptional Differences of Peanut (Arachis hypogaea L.) Seeds in the Fresh-harvest, After-ripened and Just-germinated States: insights into regulatory networks of seed dormancy-release and germination

Seed dormancy and germination are the two important traits related to plant survival and reproduction, and crop yield. To understand their regulation mechanism, it is crucial to clarify which genes or which pathways participate in the regulation of these processes. However, little information is available during the procedure of seed dormancy and germination in peanut. In this study, the seeds of the variety Luhua No.14 with non-deep dormancy were selected and its transcriptional changes at three developmental stages: the fresh-harvest (FS), the after-ripened (DS) and the just-germinated seeds (GS), were investigated by comparative transcriptomics analysis. The results showed that genes with increased transcription in DS vs FS comparison were overrepresented for oxidative phosphorylation, glycolysis pathway and tricarboxylic acid cycle (TCA), suggesting that after a period of drying storage, the intermediates stored in dry seeds were rapidly mobilized by glycolysis, TCA cycle, glyoxylate cycle, etc.; the electron transport chain accompanying with respiration has been reactivated to provide ATP for mobilization of other reserves and seed germination. In GS vs DS pairwise, dozens of the up-regulated genes were related to plant hormone biosynthesis and signal transduction, including the majority of components in auxin signal pathway, and brassinosteroid biosynthesis and signal transduction, and some GA and ABA signal transduction genes. During seeds germination, the expression of some EXPANSIN and XYLOGLUCAN ENDOTRANSGLYCOSYLASE was also significantly enhanced. To investigate the effect of different hormone during the procedure of seed germination, the contents and the differential distribution of ABA, GA, BR and IAA in cotyledon, hypocotyl and radicle, and plumule of three seed sections at different developmental stages were also detected. Combining with previous data in other species, a model of regulatory network related to peanut seed germination was developed. This model will helpful to gain further understanding of the mechanisms controlling seed dormancy and germination.

plant biology↗