A5089537299- Hippo pathway signaling and YAP/TAZ
- Supramolecular Self-Assembly in Materials
- RNA Research and Splicing
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- CAR-T cell therapy research
- Enzyme Structure and Function
- RNA modifications and cancer
- Alzheimer's disease research and treatments
- RNA Interference and Gene Delivery
- Cellular Mechanics and Interactions
- Signaling Pathways in Disease
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Glycosylation and Glycoproteins Research
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Fungal and yeast genetics research
- DNA Repair Mechanisms
- Cancer Mechanisms and Therapy
- Photosynthetic Processes and Mechanisms
- Chromatin Remodeling and Cancer
- Protein Kinase Regulation and GTPase Signaling
Nankai University
2014-2024
Collaborative Innovation Center of Chemical Science and Engineering Tianjin
2014-2022
State Key Laboratory of Medicinal Chemical Biology
2014-2022
State Key Laboratory of Chemical Engineering
2014
University of Hong Kong
2003-2007
Hong Kong University of Science and Technology
2003-2007
The tumor suppressor Merlin/NF2 functions upstream of the core Hippo pathway kinases Lats1/2 and Mst1/2, as well nuclear E3 ubiquitin ligase CRL4DCAF1. Numerous mutations Merlin have been identified in Neurofibromatosis type 2 other cancer patients. Despite more than two decades research, regulator remains unknown. Here we show by high-resolution crystal structures that Lats1/2-binding site on FERM domain is physically blocked Merlin's auto-inhibitory tail. Angiomotin binding releases...
Styling gels: The fusion protein ULD-TIP-1 (ULD=ubiquitin-like domain, TIP-1=Tax-interacting protein-1) enhances the interactions between self-assembled fibers formed by small molecules bearing a peptide that specifically binds to ULD-TIP-1. mechanical properties of resulting hydrogels (see picture) are tuned using peptides with different dissociation constants for protein. Detailed facts importance specialist readers published as "Supporting Information". Such documents peer-reviewed, but...
Self-sorting is a common phenomenon in eukaryotic cells and represents one of the versatile strategies for formation advanced functional materials; however, developing artificial self-sorting assemblies within living remains challenging. Here, we report on GSH-responsive situ peptide cancer simultaneous organelle targeting to promote combinatorial dysfunction thereby cell death. The system was created via design two peptides E3C16E6 EVMSeO derived from lipid-inspired interdigitating...
Enzyme-regulated in situ self-assembly of peptides represents one versatile strategy the creation theranostic agents, which, however, is limited by strong dependence on enzyme overexpression. Herein, we reported self-amplifying assembly precisely macrophages associated with expression for improving anti-inflammatory efficacy conventional drugs. The assembling system was created via coassembling an enzyme-responsive peptide its derivative functionalized a protein ligand. Reduction NAD(P)H...
Understanding specific protein-peptide interactions could offer a deep insight into the development of therapeutics for many human diseases. In this work, we designed and synthesized far-red/near-infrared (FR/NIR) fluorescence light-up probe (DBT-2EEGWRESAI) by simply integrating two tax-interacting protein-1 (TIP-1)-specific peptide ligands (EEGWRESAI) with one 4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole (DBT) unit. We first demonstrated that DBT is an environment-sensitive fluorophore...
Uneven distribution and local concentration of protein complexes on distinct membrane cortices is a fundamental property in numerous biological processes, including Drosophila neuroblast (NB) asymmetric cell divisions polarity general. In NBs, the fate determinant Numb forms basal crescent together with Pon segregated into daughter to initiate its differentiation. Here we discover that PTB domain, using two binding surfaces, recognizes repeating motifs within previously unrecognized mode....
Responsive hydrogels hold great potential in controllable drug delivery, regenerative medicine, sensing, etc. We introduced this study the first example of a photo-responsive protein for hydrogel formation. Based on crystal structure protein, Arabidopsis thaliana UVR8, we designed and expressed its derived UVR8-1 with hexa-peptide WRESAI. also prepared supramolecular nanofibers TIP-1 at their surface. The simple mixing these two components resulted rapid formation through specific...
Mitochondrion-targeting therapy exhibits great potential in cancer but significantly suffers from limited therapeutic efficiency. Here we report on mitochondrion-targeting supramolecular antagonist-inducing tumor cell death via simultaneously promoting cellular apoptosis and preventing survival. The antagonist was created coassembly of a pentapeptide with its two derivatives functionalized BH3 domain or the drug camptothecin (CPT). While CPT released induced decreasing mitochondrial membrane...
Abstract Oncoprotein SS18-SSX is a hallmark of synovial sarcomas. However, as part the fusion protein, SS18’s function remains unclear. Here, we depict structures both human SS18/BRG1 and yeast SNF11/SNF2 subcomplexes. Both subcomplexes assemble into heterodimers that share similar conformation, suggesting SNF11 might be homologue SS18 in chromatin remodeling complexes. Importantly, our study shows self-association intrinsically disordered region, QPGY domain, leads to liquid-liquid phase...
Abstract The highly conserved Paf1 complex (PAF1C) plays critical roles in RNA polymerase II transcription elongation and the regulation of histone modifications. It has also been implicated other diverse cellular activities, including posttranscriptional events, embryonic development cell survival maintenance stem identity. Here, we report structure human Paf1/Leo1 subcomplex within PAF1C. overall reveals that Leo1 subunits form a tightly associated heterodimer through antiparallel...
Significance Elongator is a highly conserved multiprotein complex composed of six subunits elongator protein 1 (Elp1 to -6). has been associated with various cellular activities and attracted clinical attention because its role in certain neurodegenerative diseases. To understand the mechanism assembly, we identified dimerization domain both human yeast Elp1 solved crystal structures domains. This study mechanistic analysis dimerization, which plays an essential integrity functional suggests...
Abstract The evolutionarily conserved multifunctional polymerase-associated factor 1 (Paf1) complex (Paf1C), which is composed of at least five subunits (Paf1, Leo1, Ctr9, Cdc73, and Rtf1), plays vital roles in gene regulation has connections to development human diseases. Here, we report two structures each the yeast Ctr9/Paf1 subcomplexes, assemble into heterodimers with very similar conformations, revealing an interface between tetratricopeptide repeat module Ctr9 Paf1. structure...
CD19 chimeric antigen receptor (CAR)-T therapy has shown impactful results in treatment of B-cell malignancies. However, immune recognition the murine scFv may render subsequent infusion(s) ineffective. Also, nonselective expansion both CAR-transduced and nontransduced T cells during production stage affects yield purity final products. Here, we aim to develop a humanized selective (hs) CAR solve above problems.Experimental Design: A hsCAR was designed, which incorporated short domain...
A new synergistic system combining KLVFF peptide and self-assembly chaperone can synchronize disaggregating amyloid fibrils reducing consequent toxicity.
Defective cholesterol biosynthesis in eye lens cells is often associated with cataracts; however, how genes involved are regulated remains unclear. Here, we show that Quaking (Qki) required for the transcriptional activation of lens. At transcriptome level, lens-specific Qki-deficient mice present downregulation pathway, resulting a significant reduction total level Mice Qki depletion epithelium display progressive accumulation protein aggregates, eventually leading to cataracts. Notably,...
Elongator is a multiprotein complex composed of two subcomplexes, Elp1-3 and Elp4-6. highly conserved between yeast humans plays an important role in RNA polymerase II-mediated transcriptional elongation many other processes, including cytoskeleton organization, exocytosis, tRNA modification. Here, we determined the crystal structure Elp4-6 subcomplex yeast. The overall revealed that Elp6 acts as bridge to assemble Elp4 Elp5. Detailed structural sequence analyses each subunit forms...
Special AT-rich sequence-binding protein 1 (SATB1) is a global chromatin organizer and gene expression regulator essential for T-cell development breast cancer tumor growth metastasis. The oligomerization of the N-terminal domain SATB1 critical its biological function. We determined crystal structure SATB1. Surprisingly, this resembles ubiquitin instead previously proposed PDZ domain. Our results also reveal that can form tetramer through tetramerization plays an role in binding to highly...