A5013553192- GABA and Rice Research
- Ion Transport and Channel Regulation
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Membrane-based Ion Separation Techniques
- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- RNA Research and Splicing
- Pancreatic function and diabetes
- Advanced NMR Techniques and Applications
- Photoreceptor and optogenetics research
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Photosynthetic Processes and Mechanisms
- Cellular transport and secretion
- RNA regulation and disease
- Parvovirus B19 Infection Studies
- Reproductive biology and impacts on aquatic species
- Williams Syndrome Research
- Iron Metabolism and Disorders
- Enzyme Structure and Function
- 3D Printing in Biomedical Research
University of California, Los Angeles
2016-2024
Oregon Health & Science University
2012-2014
Vollum Institute
2012-2014
Max Planck Institute of Biophysics
2011-2012
Centre National de la Recherche Scientifique
2011
Institut de Biologie Physico-Chimique
2011
Max Planck Institute of Molecular Physiology
2004-2007
Max Planck Society
2004-2005
Amphipols (APols) are short amphipathic polymers that can substitute for detergents to keep integral membrane proteins (MPs) water soluble. In this review, we discuss their structure and solution behavior; the way they associate with MPs; structure, dynamics, properties of resulting complexes. All MPs tested date form water-soluble complexes APols, biochemical stability is in general greatly improved compared detergent solutions. The functionality ligand-binding APol-trapped reviewed,...
Although the role of hydrophilic antioxidants in development hepatic insulin resistance and nonalcoholic fatty liver disease has been well studied, lipophilic remains poorly characterized. A known hydrogen peroxide scavenger is bilirubin, which can be oxidized to biliverdin then reduced back bilirubin by cytosolic reductase. Oxidation inside mitochondria must followed export cytosol, where bilirubin. Thus, putative mitochondrial exporter expected a major determinant regeneration...
Sodium-dependent glucose transporters (SGLTs) exploit sodium gradients to transport sugars across the plasma membrane. Due their role in renal sugar reabsorption, SGLTs are targets for treatment of type 2 diabetes. Current therapeutics phlorizin derivatives that contain a moiety bound an aromatic aglycon tail. Here, we develop structural models human SGLT1/2 complex with inhibitors by combining computational and functional studies. Inhibitors bind pocket tail extracellular vestibule. The...
Abstract Proteins possess a complex and dynamic structure, which is influenced by external signals may change as they perform their biological functions. We present an optical approach, distance-encoding photoinduced electron transfer (DEPET), capable of the simultaneous study protein structure function. An alternative to FRET-based methods, DEPET based on quenching small conjugated fluorophores transfer: reaction that requires contact excited fluorophore with suitable donor. This property...
Abstract Background We aimed to define the clinical and variant spectrum provide novel molecular insights into DHX30 -associated neurodevelopmental disorder. Methods Clinical genetic data from affected individuals were collected through Facebook-based family support group, GeneMatcher, our network of collaborators. investigated impact missense variants with respect ATPase helicase activity, stress granule (SG) formation, global translation, their effect on embryonic development in zebrafish....
Density gradients with increasing concentrations of cyclodextrin and detergent-destabilized liposomes are loaded detergent-solubilized membrane proteins in a new approach for reconstituting proteins. During centrifugation, the detergent is gradually replaced by lipid. This gentle method separates proteoliposomes from empty particularly suitable lipid reconstitution large, fragile Membrane account about 20–30 % protein-encoding genes genomes all living organisms.2 Their fundamental importance...
Using primers against conserved regions of mammalian Na(+)-d-glucose cotransporters (SGLT), a cDNA was cloned from the kidney spiny dogfish shark (Squalus acanthias). On basis comparison amino acid sequence, membrane topology, and putative glycosylation phosphorylation sites, could be shown to belong family sglt genes. Indeed, Na(+)-dependent d-glucose uptake demonstrated after expression gene in Xenopus laevis oocytes. In dendrogram, SGLT has high homology SGLT2. Computer analysis revealed...
Smith-Kingsmore syndrome (SKS) is a rare neurodevelopmental disorder characterized by macrocephaly/megalencephaly, developmental delay, intellectual disability, hypotonia, and seizures. It caused dominant missense mutations in MTOR . The pathogenicity of novel variants patients with disorders can be difficult to determine the mechanism which cause disease remains poorly understood. We report 7 SKS 4 describe their phenotypes. perform vitro functional analyses confirm activation interrogate...
Abstract Sodium-dependent glucose transporters (SGLTs) couple a downhill Na + ion gradient to actively transport sugars. Here, we investigate the impact of membrane potential on vSGLT structure and function using sugar uptake assays, double electron-electron resonance (DEER), electrostatic calculations, kinetic modeling. Negative potentials, as present in all cell types, shift conformational equilibrium towards an outward-facing conformation, leading increased rates. Electrostatic...
Studies on membrane vesicles from the kidney of Leucoraja erinacea suggested sole presence a sodium-D-glucose cotransporter type 1 involved in renal D-glucose reabsorption. For molecular characterization this transport system, an mRNA library was screened with primers directed against conserved regions human sglt1. A cDNA cloned whose nucleotide and derived amino acid sequence revealed high homology to sodium glucose (SGLT1). Xenopus laevis oocytes injected respective cRNA showed...
The voltage-dependent anion channel (VDAC) is a crucial mitochondrial protein that facilitates ion and metabolite exchange between mitochondria the cytosol. Initially characterized over three decades ago, structure of VDAC-1 was resolved in 2008, revealing novel β-barrel architecture. This study presents first room-temperature crystal mouse (mVDAC-1), which significant step toward understanding channel’s gating mechanism. new structure, obtained at 3.3 Å resolution, demonstrates notable...
Dichtegradienten mit Cyclodextrin und tensiddestabilisierten Liposomen in zunehmenden Konzentrationen wurden einem neuen Ansatz zur Rekonstitution von Membranproteinen tensidsolubilisierten beladen. Während des Zentrifugierens wird das Tensid nach durch Lipid ersetzt. Diese milde Methode trennt Proteoliposomen leeren ist besonders für die Lipidrekonstitution großer, fragiler Membranproteine geeignet. Membrane proteins account for about 20–30 % of the protein-encoding genes genomes all living...
Abstract Background We aimed to define the clinical and mutational spectrum, provide novel molecular insights into DHX30 -associated neurodevelopmental disorder. Methods Clinical genetic data from affected individuals were collected through family support group, GeneMatcher our network of collaborators. investigated impact missense variants with respect ATPase helicase activity, stress granule (SG) formation, global translation, their effect on embryonic development in zebrafish. SG...