A5008752336- Lipid Membrane Structure and Behavior
- Drug Transport and Resistance Mechanisms
- Cholesterol and Lipid Metabolism
- Ubiquitin and proteasome pathways
- Nuclear Structure and Function
- RNA Interference and Gene Delivery
- Telomeres, Telomerase, and Senescence
- Cellular transport and secretion
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Endoplasmic Reticulum Stress and Disease
- Peroxisome Proliferator-Activated Receptors
- Cell death mechanisms and regulation
- Lipid metabolism and biosynthesis
- Complement system in diseases
- Animal Virus Infections Studies
- Sphingolipid Metabolism and Signaling
- Muscle Physiology and Disorders
- Autophagy in Disease and Therapy
- Nanopore and Nanochannel Transport Studies
- Renal Diseases and Glomerulopathies
- Insect Resistance and Genetics
- Advanced Electron Microscopy Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- Histone Deacetylase Inhibitors Research
Hormel (United States)
2020-2025
University of Minnesota
2020-2025
Mayo Clinic
2024-2025
WinnMed
2025
Ho Chi Minh City University of Technology and Education
2023
Aarhus University
2015-2022
Soongsil University
2013-2022
Aarhus University Hospital
2022
Abstract ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it able recognize transport wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures lipid-embedded human conformationally distinct apo-, substrate-bound, inhibitor-bound, nucleotide-trapped states at 3.4–3.9 Å resolution, the absence stabilizing antibodies or mutations. The substrate-binding site located within one half...
In human cells, thousands of predominantly neuronal genes are regulated by the repressor element 1 (RE1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF). REST/NRSF represses these in stem cells and non-neuronal tethering corepressor complexes. Aberrant expression intracellular localization associated with cancer neurodegeneration humans. To date, detailed molecular analyses its C-terminal complex have been hampered largely lack sufficient amounts purified...
Phospholipid extrusion by ABC subfamily A (ABCA) exporters is central to cellular physiology, although the specifics of underlying substrate interactions and transport mechanisms remain poorly resolved at molecular level. Here we report cryo-EM structures lipid-embedded human ABCA7 in an open state a nucleotide-bound, closed resolutions between 3.6 4.0 Å. The former reveals ordered patch bilayer lipids traversing transmembrane domain (TMD), while latter lipid-free, TMD with small...
Significance Apaf-1 interacting protein (APIP) inhibits two main types of programmed cell death: apoptosis and pyroptosis. In addition, APIP is a 5-methylthioribulose-1-phosphate dehydratase (MtnB) in the methionine salvage pathway. We verified its enzymatic activity directly through an enzyme assay determined high-resolution structure. Furthermore, we explored relationship between distinct functions APIP/MtnB, death inhibition salvage, that it as inhibitor independently MtnB for apoptosis,...
Abstract The peroxisomal very long chain fatty acid (VLCFA) transporter ABCD1 is central to catabolism and lipid biosynthesis. Its dysfunction underlies toxic cytosolic accumulation of VLCFAs, progressive demyelination, neurological impairments including X-linked adrenoleukodystrophy (X-ALD). We present cryo-EM structures in phospholipid nanodiscs a nucleotide bound conformation open the lumen an inward facing cytosol at up 3.5 Å resolution, revealing details its transmembrane cavity ATP...
The hexameric ATPase p97 has been implicated in diverse cellular processes through interactions with many different adaptor proteins at its N-terminal domain. Among these, the Ufd1-Npl4 heterodimer is a major adaptor, and p97-Ufd1-Npl4 complex plays an essential role endoplasmic reticulum-associated degradation (ERAD), acting as segregase that translocates ubiquitinated client protein from ER membrane into cytosol for proteasomal degradation. We determined crystal structure of domain SHP box...
Abstract ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, its mechanisms of poly-specific substrate recognition transport remain poorly resolved. Here we present cryo-EM structures lipid embedded human apo, substrate-bound, inhibitor-bound, nucleotide-trapped states at 3.4-3.9 Å resolution without using stabilizing antibodies or mutations each revealing distinct conformation. The binding site located within one half the...
In vitro assessment of lipid intermembrane transfer activity by cellular proteins typically involves measurement either radiolabeled or fluorescently labeled trafficking between vesicle model membranes. Use bilayer vesicles in assays usually comes with inherent challenges because complexities associated the preparation and their rather short "shelf life". Such issues necessitate laborious task fresh to achieve high quality, precision, reproducibility. To overcome these limitations, we have...
Abstract Phospholipid extrusion by ABC subfamily A (ABCA) exporters is central to cellular physiology, although the specifics of underlying substrate interactions and transport mechanisms remain poorly resolved at molecular level. Here we report cryo-EM structures lipid-embedded human ABCA7 in an open state a nucleotide-bound, closed resolutions between 3.6-4.0 Å. The former reveals ordered patch bilayer lipids traversing transmembrane domain (TMD), while latter lipid-free, TMD with small...
// Abhijit Chakraborty 1 , 2 Faisal Aziz Eunmiri Roh Le Thi My Raja Dey Tianshun Zhang Moeez G. Rathore Aalekhya Sharma Biswas 3 Ann M. Bode and Zigang Dong 4 The Hormel Institute, University of Minnesota, Austin, MN 55912, USA Immunology, Allergy Rheumatology Section, Baylor College Medicine, Houston, TX 77030, Pediatric Gastroenterology Liver Center, Texas, Zhengzhou University, Zhengzhou, Henan Province 450052, China Correspondence to: Dong, email: dongzg@zzu.edu.cn Keywords: TIMELESS;...
Various methods have been developed to generate phosphoglyceride liposomes. Approaches resulting in homogeneous populations of unilamellar bilayer vesicles are generally preferred mimic various cell membrane situations, as well optimize aqueous solute trapping efficiency using the least amount lipid for biotechnological purposes. Most time-consuming, often tedious, or require specialized equipment, and produce with limited shelf-life at room temperature cold storage. Herein, we describe a...
The tripartite partition defect (PAR) polarity complex, which includes the proteins PAR3, atypical protein kinase C (aPKC), and PAR6, is a major regulator of cellular polarity. It highly conserved expressed in various tissues. Its largest component, controls protein-protein interactions PAR complex with variety interaction partners, PAR3 self-association critical for formation filament-like structures. However, little known about structure complex. Here, we purified non-filamentous aPKC-PAR6...
Abstract The peroxisomal very long chain fatty acid (VLCFA) transporter ABCD1 is central to cellular catabolism and lipid biosynthesis. Its dysfunction underlies toxic cytosolic accumulation of VLCFAs, progressive nervous system demyelination, neurological impairments including the potentially fatal disease X-linked adrenoleukodystrophy (X-ALD). Molecular details underlying substrate recognition transport by are poorly understood. Here we determined cryo-EM structures in phospholipid...
Telomeres protect chromosome ends and determine the replication potential of dividing cells. The canonical telomere sequence TTAGGG is synthesized by telomerase holoenzyme, which maintains length in proliferative stem Although core components are well-defined, mechanisms regulation still under investigation. We report a novel role for Src family kinase Fyn, disrupts maintenance cells phosphorylating scaffold protein Menin. found that Fyn knockdown prevented erosion human mouse cells,...
Abstract Telomeres protect chromosome ends and determine the proliferative potential of cells. The canonical telomere sequence TTAGGG is synthesized by telomerase holoenzyme, which maintains length in stem Although core components are well defined, many aspects regulation poorly understood. We report a novel role for Src family kinase Fyn, interrupts maintenance cells negatively regulating assembly. that Fyn promotes SUMOylation scaffold protein menin at lysine 609 (K609) phosphorylating...
ATP-binding cassette subfamily B1 (ABCB1) is a polyspecific membrane transport protein that holds tremendous physiological, pharmacological, and clinical relevance for its role in cellular detoxification, mediation of drug pharmacokinetics, acquired multidrug resistance.Here, we report cryo-electron microscopy (cryo-EM) structures nanodisc reconstituted human ABCB1 hitherto unseen collapsed conformation with closed transmembrane pathway closely spaced but separated NBDs at 3.5 Å...