A5012616923- Autophagy in Disease and Therapy
- Receptor Mechanisms and Signaling
- Drug Transport and Resistance Mechanisms
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- DNA and Nucleic Acid Chemistry
- Trace Elements in Health
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Polyamine Metabolism and Applications
- Cancer, Stress, Anesthesia, and Immune Response
- Pancreatic function and diabetes
- Nanoplatforms for cancer theranostics
- Cancer Research and Treatments
- Amino Acid Enzymes and Metabolism
- RNA Research and Splicing
- Signaling Pathways in Disease
- Protein Structure and Dynamics
- Endoplasmic Reticulum Stress and Disease
- Ion Transport and Channel Regulation
- Genetics and Neurodevelopmental Disorders
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Nitric Oxide and Endothelin Effects
Southern University of Science and Technology
2022-2025
China Pharmaceutical University
2024
Shenzhen University
2022
Shenzhen University Health Science Center
2021
Adenosine deaminase acting on RNA (ADAR) proteins, which mediate adenosine-to-inosine editing of double-stranded ribonucleic acid (dsRNA) substrates, play essential roles in balancing innate immunity. Using cryogenic electron microscopy, we solved the structure Caenorhabditis elegans ADR-2-ADBP-1 complex (stoichiometric ratio, 2:2), is an asymmetric ADR-2 dimer with one site blocked by other ADR-2. Unexpectedly, dsRNA recruitment triggered dissociation dimer, exposing more competent sites....
Abstract Dysregulation of polyamine homeostasis strongly associates with human diseases. ATP13A2, which is mutated in juvenile-onset Parkinson’s disease and autosomal recessive spastic paraplegia 78, a transporter critical role balancing the concentration between lysosome cytosol. Here, to better understand ATP13A2-mediated transport, we use single-particle cryo-electron microscopy solve high-resolution structures ATP13A2 six intermediate states, including putative E2 structure for P5...
Abstract Human multidrug resistance protein 4 (hMRP4, also known as ABCC4), with a representative topology of the MRP subfamily, translocates various substrates across membrane and contributes to development resistance. However, underlying transport mechanism hMRP4 remains unclear due lack high-resolution structures. Here, we use cryogenic electron microscopy (cryo-EM) resolve its near-atomic structures in apo inward-open ATP-bound outward-open states. We capture PGE1 substrate-bound...
MRGPRX1, a Mas-related GPCR (MRGPR), is key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 CNF-Tx2. These reveal shallow orthosteric pocket its conformational plasticity sensing multiple different peptidic allergens. Distinct from MRGPRX2, contains unique feature at extracellular ends TM3 TM4 accommodate C-terminal "RF/RY"...
To accomplish concerted physiological reactions, nature has diversified functions of a single hormone at least two primary levels: 1) Different receptors recognize the same hormone, and 2) different cellular effectors couple to hormone–receptor pair [R.P. Xiao, Sci STKE 2001 , re15 (2001); L. Hein, J. D. Altman, B.K. Kobilka, Nature 402 181–184 (1999); Y. Daaka, M. Luttrell, R. Lefkowitz, 390 88–91 (1997)]. Not only these questions lie in heart actions receptor signaling but also dissecting...
Abstract Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, design inhibitory could block entry into transport pathway. We also identify a regulatory motif, comprising positively charged cluster hydrophobic...
Opioids are a potential adjuvant treatment for certain cancers; while they primarily used to relieve chronic pain, these drugs may also affect cancer progression and recurrence. Dezocine is one opioid commonly in China, but its effects on cells unknown. Here, we demonstrated the inhibitory effect of dezocine triple-negative breast (TNBC) cells, determined underlying molecular mechanism. We found that suppressed cell proliferation, migration invasion, induced apoptosis TNBC cells. Xenograft...
Abstract Human elaC ribonuclease Z 2 (ELAC2) removes the 3′ trailer of precursor transfer ribonucleic acid (pre-tRNA). Mutations in ELAC2 are highly associated with development prostate cancer and hypertrophic cardiomyopathy. However, catalytic mechanism remains unclear. We determined cryogenic electron microscopy structures human various states, including apo, pre-tRNA–bound tRNA-bound which enabled us to identify structural basis for its binding pre-tRNA cleavage trailer. Notably,...
Abstract Dezocine, a dual agonist and antagonist of the μ-opioid receptor κ-opioid receptor, is widely used as an analgesic in China. At present, there are few studies on anti-tumor effects dezocine, most which to treat cancer pain. However, it has recently been reported that dezocine can induce apoptosis triple negative breast cells. Dezocine may have some activity, but effect potential mechanism treatment other types remain be fully studied. The purpose present study was investigate human...