A5061459684- Lipid metabolism and biosynthesis
- Cholesterol and Lipid Metabolism
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Crystallography and molecular interactions
- Hedgehog Signaling Pathway Studies
- Ubiquitin and proteasome pathways
- Viral Infections and Outbreaks Research
- Caveolin-1 and cellular processes
- Animal Genetics and Reproduction
- Protein Structure and Dynamics
- Calcium signaling and nucleotide metabolism
- Crystallization and Solubility Studies
- Diet, Metabolism, and Disease
- RNA Research and Splicing
- Lysosomal Storage Disorders Research
- Photosynthetic Processes and Mechanisms
- Neonatal Health and Biochemistry
- Viral Infectious Diseases and Gene Expression in Insects
- X-ray Diffraction in Crystallography
- Genomic variations and chromosomal abnormalities
- Nitrogen and Sulfur Effects on Brassica
- Chromatin Remodeling and Cancer
Yangzhou University
2024-2025
University of Science and Technology of China
2022-2025
Yale University
2022
Hefei National Center for Physical Sciences at Nanoscale
2022
Princeton University
2018-2021
Center for Life Sciences
2016-2018
Tsinghua University
2016-2018
State Key Laboratory of Membrane Biology
2016
Nanjing Tech University
2003
The first step in Hedgehog signaling (Hh) pathway is important embryogenesis; overactivation associated with cancer. Central to the membrane receptor Patched 1 (Ptch1), which indirectly inhibits a G protein–coupled called Smoothened. This inhibition relieved when Ptch1 binds secreted protein Hh. Gong et al. report cryo–electron microscopy structures of human alone and complex its Hh ligand at 3.9 3.6 Å, respectively. Both include two steroid-shaped densities, mutational analysis indicates...
The Hedgehog (Hh) pathway controls embryonic development and postnatal tissue maintenance regeneration. Inhibition of Hh receptor Patched (Ptch) by the ligands relieves suppression signaling cascades. Here, we report cryo-EM structure tetrameric Ptch1 in complex with palmitoylated N-terminal domain human Sonic hedgehog (ShhNp) at a 4:2 stoichiometric ratio. shows that four protomers are organized as loose dimer dimers. Each binds to one ShhNp through two distinct inhibitory interfaces,...
A cellular cholesterol sensor Cholesterol levels in cells are controlled by the sterol regulatory element–binding protein (SREBP) pathway. When cell has sufficient cholesterol, transcription factor that regulates metabolism is sequestered at endoplasmic reticulum membrane, but when depleted, released to activate expression of genes involved synthesis and uptake. Yan et al. determined structure a central complex human SREBP containing proteins Scap Insig-2. These two membrane-embedded undergo...
Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are two primary components of the eukaryotic membrane play essential roles in maintenance integrity, lipid droplet biogenesis, autophagosome formation, lipoprotein formation secretion. Choline/ethanolamine phosphotransferase 1 (CEPT1) catalyzes last step biosynthesis PC PE Kennedy pathway by transferring substituted phosphate group from CDP-choline/ethanolamine to diacylglycerol. Here, we present cryo-EM structures human CEPT1 its...
High serum urate levels are the major risk factor for gout. URAT1, primary transporter absorption in kidneys, is well known as an anti-hyperuricemia drug target. However, clinical application of URAT1-targeted drugs limited because their low specificity and severe side effects. The lack structural information impedes elucidation transport mechanism development new drugs. Here, we present cryoelectron microscopy (cryo-EM) structures human URAT1(R477S), its complex with urate, closely related...
The sterol regulatory element-binding protein (SREBP) pathway monitors the cellular cholesterol level through sterol-regulated association between SREBP cleavage-activating (Scap) and insulin-induced gene (Insig). Despite structural determination of Scap Insig-2 complex bound to 25-hydroxycholesterol, luminal domains remain unresolved. In this study, combining cryogenic electron microscopy (cryo-EM) analysis artificial intelligence-facilitated prediction, we report structure human...
The lysosome serves as an essential nutrient-sensing hub within the cell, where mechanistic target of rapamycin complex 1 (mTORC1) is activated. Lysosomal cholesterol signaling (LYCHOS), a membrane protein, has been identified sensor that couples concentration to mTORC1 activation. However, molecular basis unknown. Here, we determine cryo-electron microscopy (cryo-EM) structure human LYCHOS at resolution 3.1 Å, revealing cholesterol-like density interface between permease and G-protein...
Insulin is an important component of stem cell cultures; however, its role in the proliferation avian primordial germ cells (PGCs) unknown. The PGCs cultures varies and growth factors signaling pathways necessary to induce chickens are Therefore, we conducted present study investigate effect insulin on survival PGCs. In this study, observed that under culture system, proliferate presence insulin, but do not absence insulin. Furthermore, insulin-lacking media, expression pluripotency genes,...
In the field of genetic breeding, primordial germ cells (PGCs) have become essential for gene editing and improvement due to their unique developmental potential characteristics. However, low proliferation efficiency instability culture systems pose significant challenges, severely limiting application PGCs in breeding. this study, biological effects ovotransferrin on chicken PGCs, focusing its role regulating key cellular processes. Treatment with 0.5 mg/ml significantly promoted cell...
Sterol regulatory element-binding protein (SREBP) transcription factors are master regulators of cellular lipid homeostasis in mammals and oxygen-responsive hypoxic adaptation fungi. SREBP C-terminus binds to the WD40 domain cleavage-activating (SCAP), which confers sterol regulation by controlling ER-to-Golgi transport SREBP-SCAP complex access activating proteases Golgi. Here, we biochemically structurally show that carboxyl terminal domains (CTD) Sre1 Scp1, fission yeast SCAP, form a...
Avian primordial germ cells (PGCs) are important culture for the production of transgenic chickens and preservation genetic resources endangered species; however, culturing these in vitro proves challenging. Although proliferation chicken PGCs is dependent on insulin, underlying molecular mechanisms remain unclear. In present study, we explored expression PI3K/AKT signaling pathway PGCs, investigated its effects PGC self-renewal biological properties, identified mechanisms. Our findings...
The Ebola virus (EBOV) has emerged as a significant global health concern, notably during the 2013–2016 outbreak in West Africa. Despite clinical approval of two EBOV antibody drugs, there is an urgent need for more diverse and effective antiviral along with comprehensive understanding viral-host interactions. In this study, we harnessed biologically contained EBOVΔVP30-EGFP cell culture model which could recapitulate entire viral life cycle, to conduct genome-wide CRISPR/Cas9 screen....
The sterol regulatory element-binding protein (SREBP) and SREBP cleavage-activating (SCAP) are central players in the pathway, which control cellular lipid homeostasis. SCAP binds to through their carboxyl (C) domains escorts from endoplasmic reticulum Golgi upon depletion. A conserved with homologues of being Sre1 Scp1, was identified fission yeast Schizosaccharomyces pombe. Here we report vitro reconstitution complex between C Scp1 as well crystal structure WD40 domain at 2.1 Å resolution....
Abstract The Hedgehog (Hh) pathway controls embryonic development and postnatal tissue maintenance regeneration. Inhibition of oligomeric Hh receptor Patched (Ptch) by the secreted post-translationally modified ligand relieves suppression signaling cascades. Here, we report cryo-EM structure tetrameric Ptch1 in complex with palmitoylated N-terminal domain human Sonic hedgehog (ShhNp). shows that four protomers are organized as a loose dimer dimers each binds to one ShhNp through two distinct...
Summary Acyl-coenzyme A: cholesterol acyltransferases (ACATs) catalyze acyl transfer from acyl-coenzyme A (CoA) to generate cholesteryl ester, which is the primary form for cellular storage and plasma transport of cholesterol. Because their close relationship with metabolism, ACATs represent potential drug target treatment atherosclerosis other cholesterol-related disorders. Here we present cryo-EM structure human ACAT1 at 3.3 Å resolution dimer dimers 3.0 a dimer. Each protomer consists...
Diderm bacteria, characterized by an additional lipid membrane layer known as the outer membrane, fold their proteins (OMPs) via β-barrel assembly machinery (BAM) complex. Understanding how BAM complex, particularly its key component BamA, assists in OMP folding remains crucial bacterial cell biology. Recent research has focused primarily on structural and functional characteristics of BamA within Gracilicutes clade, such <i>Escherichia coli</i> (<i>E. coli</i>)....