A5076426077- SARS-CoV-2 and COVID-19 Research
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- COVID-19 Clinical Research Studies
- Bone and Dental Protein Studies
- Protein Tyrosine Phosphatases
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- Bacillus and Francisella bacterial research
- Galectins and Cancer Biology
- Microtubule and mitosis dynamics
- Enzyme Structure and Function
- Lysosomal Storage Disorders Research
- Viral Infections and Immunology Research
- vaccines and immunoinformatics approaches
- Phytase and its Applications
- Complement system in diseases
- Plant Reproductive Biology
- Trace Elements in Health
- Plant Molecular Biology Research
- Mosquito-borne diseases and control
- T-cell and B-cell Immunology
- Calcium signaling and nucleotide metabolism
Peking University
2016-2025
Center for Life Sciences
2016-2024
King Center
2017-2023
Center for Interdisciplinary Studies
2022
State Key Laboratory of Protein and Plant Gene Research
2021
Wuhan Polytechnic University
2021
Nanjing University of Posts and Telecommunications
2020
University of California, San Diego
2010-2015
University of Michigan
2007-2011
University of California, Los Angeles
2011
The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening1,2 to determine profiles RBD escaping for 247 human anti-RBD and show that can be classified by unsupervised clustering into six epitope groups (A-F)-a grouping is highly concordant with knowledge-based structural classifications3-5. Various single...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage 1 . The receptor binding immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons spike proteins, we show that (BA.4 are hereafter referred collectively to as BA.4/BA.5) similar affinities for angiotensin-converting enzyme (ACE2) receptor. Of note,...
Protein phosphorylation is a fundamental mechanism regulating nearly every aspect of cellular life. Several secreted proteins are phosphorylated, but the kinases responsible unknown. We identified family atypical protein that localize within Golgi apparatus and secreted. Fam20C appears to be casein kinase phosphorylates secretory pathway S-x-E motifs. caseins several implicated in biomineralization, including small integrin-binding ligand, N-linked glycoproteins (SIBLINGs). Consequently,...
In flowering plants, fertilization requires complex cell-to-cell communication events between the pollen tube and female reproductive tissues, which are controlled by extracellular signaling molecules interacting with receptors at surface. We found that two such in Arabidopsis, BUPS1 BUPS2, their peptide ligands, RALF4 RALF19, tube-expressed required to maintain integrity. BUPS2 interact ANXUR1 ANXUR2 via ectodomains, both sets of bind RALF19. These receptor-ligand interactions competition...
The family with sequence similarity 20, member C (Fam20C) has recently been identified as the Golgi casein kinase. Fam20C phosphorylates secreted proteins on Ser-x-Glu/pSer motifs and loss-of-function mutations in kinase cause Raine syndrome, an often-fatal osteosclerotic bone dysplasia. is potentially upstream regulator of phosphate-regulating hormone fibroblast growth factor 23 (FGF23), because humans FAM20C KO mice develop hypophosphatemia due to increase full-length, biologically active...
Significance Baicalin is a major flavonoid component from the herbal medicine Scutellaria baicalensis that has been shown to have an antisteatosis effect. Through quantitative chemoproteomic profiling, we discovered baicalin acts as natural allosteric activator of carnitine palmitoyltransferase 1 (CPT1), rate-limiting enzyme fatty acid β-oxidation (FAO). By directly binding CPT1 and activating its activity accelerate degradation, can significantly ameliorate symptoms associated with hepatic...
Abstract SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal (NTD). Here we report humoral response to circulating variants, such as 501Y.V2 (B.1.351), of plasma neutralizing antibodies (NAbs) elicited CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) natural infection. Among 86 potent NAbs identified high-throughput single-cell VDJ sequencing peripheral blood mononuclear cells from vaccinees convalescents, near half...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad candidate selection methods needed. Here, we describe a rational approach for identifying RBD-targeting SARS-CoV-2 cocktails. Based on high-throughput epitope determination, propose drugs...
Abstract SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.2 1 . The new variants’ receptor binding immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 BA.4/BA.5 comparable ACE2-binding affinities to BA.2. Importantly, display stronger neutralization than against the plasma from 3-dose vaccination and, most strikingly, post-vaccination BA.1 infections. To delineate...
The emergence of Omicron lineages and descendent subvariants continues to present a severe threat the effectiveness vaccines therapeutic antibodies. We have previously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by mRNA is associated with surge in breakthrough infections. Here, we further show intramuscular and/or inactivated cannot sufficiently boost secretory IgA uninfected individuals, particularly against variant. thus engineered characterized...
Curcumin, the active ingredient in Curcuma longa, has been medicinal use since ancient times. However, therapeutic targets and signaling cascades modulated by curcumin have enigmatic despite extensive research. Here we identify dual-specificity tyrosine-regulated kinase 2 (DYRK2), a positive regulator of 26S proteasome, as direct target curcumin. Curcumin occupies ATP-binding pocket DYRK2 cocrystal structure, it potently specifically inhibits over 139 other kinases tested vitro. As result,...
Reproductive isolation is a prerequisite for speciation. Failure of communication between female tissues the pistil and paternal pollen tubes imposes hybridization barriers in flowering plants. Arabidopsis thaliana LURE1 (AtLURE1) peptides their male receptor PRK6 aid attraction growing tube to ovule. Here, we report that knockout entire AtLURE1 gene family did not affect fertility, indicating AtLURE1-PRK6-mediated signaling required successful fertilization within one species. AtLURE1s...
Immunoglobulin M (IgM) plays a pivotal role in both humoral and mucosal immunity. Its assembly transport depend on the joining chain (J-chain) polymeric immunoglobulin receptor (pIgR), but underlying molecular mechanisms of these processes are unclear. We report cryo-electron microscopy structure Fc region human IgM complex with J-chain pIgR ectodomain. The IgM-Fc pentamer is formed asymmetrically, resembling hexagon missing triangle. tailpieces pack into an amyloid-like to stabilize...
DNA replication-coupled (RC) nucleosome assembly is mediated by histone chaperones and fundamental for epigenetic inheritance maintenance of genomic integrity. The mechanisms that promote this process are only partially understood. Here, we show the chaperone FACT (facilitates chromatin transactions), consisting Spt16 Pob3, promotes newly synthesized H3-H4 deposition. We describe an allele (spt16-m) has a defect in binding to impairs their deposition onto DNA. Consistent with direct role RC...
Although numerous extracellular phosphoproteins have been identified, the protein kinases within secretory pathway only recently discovered, and their regulation is virtually unexplored. Fam20C physiological Golgi casein kinase, which phosphorylates many secreted proteins critical for proper biomineralization. Fam20A, a paralog, essential enamel formation, but biochemical function of Fam20A unknown. Here we show that potentiates kinase activity promotes phosphorylation matrix in vitro cells....
Significance Proteoglycans are cellular proteins modified with long chains of repeating sugar residues connected to serine within the protein core by a short tetrasaccharide linker. perform critical functions such as formation extracellular matrix, binding diverse array molecules, and regulation cell motility, adhesion, cell–cell communication. We show here that family sequence similarity 20, member B (Fam20B) is xylose kinase phosphorylates residue proteoglycan linkage. Xylose...
The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening1,2 to determine profiles RBD escaping for 247 human anti-RBD and show that can be classified by unsupervised clustering into six epitope groups (A–F)—a grouping is highly concordant with knowledge-based structural classifications3–5. Various single...
Abstract Ethylene is an important phytohormone that promotes the ripening of fruits and senescence flowers thereby reducing their shelf lives. Specific ethylene biosynthesis inhibitors would help to decrease postharvest loss. Here, we identify pyrazinamide (PZA), a clinical drug used treat tuberculosis, as inhibitor in Arabidopsis thaliana , using chemical genetics approach. PZA converted pyrazinecarboxylic acid (POA) plant cells, suppressing activity 1-aminocyclopropane-1-carboxylic oxidase...
Abstract The SARS-CoV-2 B.1.1.529 variant (Omicron) contains 15 mutations on the receptor-binding domain (RBD). How Omicron would evade RBD neutralizing antibodies (NAbs) requires immediate investigation. Here, we used high-throughput yeast display screening 1,2 to determine escaping mutation profiles for 247 human anti-RBD NAbs and showed that could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications 3-5 ....