A5058547125- Calcium signaling and nucleotide metabolism
- Autophagy in Disease and Therapy
- Ion Channels and Receptors
- Legionella and Acanthamoeba research
- Piperaceae Chemical and Biological Studies
- Pineapple and bromelain studies
- Neonatal Health and Biochemistry
- Erythrocyte Function and Pathophysiology
- Cancer Research and Treatments
- Photosynthetic Processes and Mechanisms
- Cytomegalovirus and herpesvirus research
- Plant Molecular Biology Research
- Ion channel regulation and function
- Biomedical Research and Pathophysiology
- Endoplasmic Reticulum Stress and Disease
- Rabies epidemiology and control
- Photoreceptor and optogenetics research
- Heme Oxygenase-1 and Carbon Monoxide
- Cellular transport and secretion
- Genetics, Aging, and Longevity in Model Organisms
Howard Hughes Medical Institute
2021-2024
The University of Texas Southwestern Medical Center
2021-2024
Purdue University West Lafayette
2018-2020
Transient receptor potential mucolipin 1 (TRPML1) is a Ca2+-permeable, nonselective cation channel ubiquitously expressed in the endolysosomes of mammalian cells and its loss-of-function mutations are direct cause type IV mucolipidosis (MLIV), an autosomal recessive lysosomal storage disease. TRPML1 ligand-gated that can be activated by phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] as well some synthetic small-molecule agonists. Recently, rapamycin has also been shown to directly bind...
Retrograde vesicle trafficking pathways are responsible for returning membrane-associated components from endosomes to the Golgi apparatus and endoplasmic reticulum (ER), they critical maintaining organelle identity, lipid homeostasis, many other cellular functions. The retrograde transport pathway has emerged as an important target intravacuolar bacterial pathogens. opportunistic pathogen Legionella pneumophila exploits both secretory recycling branches of intracellular proliferation. Its...
Significance How membrane potential drives conformational change at the voltage-sensing domain (VSD) and regulates channel gating is a central theme for voltage-gated ion channels. To elucidate voltage-gating mechanisms, one needs to capture VSD structures in both activated state resting state, latter of which difficult obtain because VSDs tend adopt an absence most vitro experiments. Here, we determined AtTPC1 closed conformation with VSDII unbound EF-hand partially open Ca 2+ -activated...
Abstract The Legionella pneumophila effector MavC is a transglutaminase that carries out atypical ubiquitination of the host ubiquitin (Ub)‐conjugation enzyme UBE2N by catalyzing formation an isopeptide bond between Gln40 Ub and Lys92 , which leads to inhibition signaling in NF‐κB pathway. In absence UBE2N, deamidates at or catalyzes self‐ubiquitination. However, mechanisms underlying these enzymatic activities are poorly understood molecular level. This study reports structure MavC–UBE2N–Ub...
Abstract The otopetrin (OTOP) proteins were recently characterized as extracellular proton-activated proton channels. Several recent OTOP channel structures demonstrated that the channels form a dimer with each subunit adopting double-barrel architecture. However, structural mechanisms underlying some basic functional properties of remain unresolved, including pH activation, conducting pathway, and rapid desensitization. In this study, we performed characterization Caenorhabditis elegans...
Transient Receptor Potential Mucolipin 1 (TRPML1) is a lysosomal cation channel whose loss-of-function mutations directly cause the storage disorder mucolipidosis type IV (MLIV). TRPML1 can be allosterically regulated by various ligands including natural lipids and small synthetic molecules undergoes global movement propagated from ligand-induced local conformational changes upon activation. In this study, we identified functionally critical residue, Tyr404, at C-terminus of S4 helix, to...
Abstract Transient Receptor Potential Mucolipin 1 (TRPML1) is a lysosomal cation channel whose loss-of-function mutations directly cause the storage disorder mucolipidosis type IV (MLIV). TRPML1 can be allosterically regulated by various ligands including natural lipids and small synthetic molecules undergoes global movement propagated from ligand-induced local conformational changes upon activation. In this study, we identified functionally critical residue, Tyr404, at C-terminus of S4...
Transient Receptor Potential Mucolipin 1 (TRPML1) is a lysosomal cation channel whose loss-of-function mutations directly cause the storage disorder mucolipidosis type IV (MLIV). TRPML1 can be allosterically regulated by various ligands including natural lipids and small synthetic molecules undergoes global movement propagated from ligand-induced local conformational changes upon activation. In this study, we identified functionally critical residue, Tyr404, at C-terminus of S4 helix, to...
Transient Receptor Potential Mucolipin 1 (TRPML1) is a lysosomal cation channel whose loss-of-function mutations directly cause the storage disorder mucolipidosis type IV (MLIV). TRPML1 can be allosterically regulated by various ligands including natural lipids and small synthetic molecules undergoes global movement propagated from ligand-induced local conformational changes upon activation. In this study, we identified functionally critical residue, Tyr404, at C-terminus of S4 helix, to...
Transient Receptor Potential Mucolipin 1 (TRPML1) is a lysosomal cation channel whose loss-of-function mutations directly cause the storage disorder mucolipidosis type IV (MLIV). TRPML1 can be allosterically regulated by various ligands including natural lipids and small synthetic molecules undergoes global movement propagated from ligand-induced local conformational changes upon activation. In this study, we identified functionally critical residue, Tyr404, at C-terminus of S4 helix, to...
Summary The Legionella pneumophila effector MavC is a transglutaminase that carries out atypical ubiquitination of the ubiquitin (Ub) E2 conjugation enzyme UBE2N by catalyzing formation an isopeptide bond between Gln40 Ub and Lys92 (or to less extent, Lys94) UBE2N, which results in inhibition signaling NF-κB pathway. In absence deamidates at or catalyzes self-ubiquitination. However, mechanisms underlying these enzymatic activities are not fully understood molecular level. this study, we...