A5087524332- Enzyme Structure and Function
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Advanced Electron Microscopy Techniques and Applications
- T-cell and B-cell Immunology
- Toxin Mechanisms and Immunotoxins
- Hemophilia Treatment and Research
- Platelet Disorders and Treatments
- Protein Structure and Dynamics
- Iron Metabolism and Disorders
- Helicobacter pylori-related gastroenterology studies
- Cellular transport and secretion
- Veterinary medicine and infectious diseases
- Electron and X-Ray Spectroscopy Techniques
- Immune Cell Function and Interaction
- Blood groups and transfusion
- Galectins and Cancer Biology
- Receptor Mechanisms and Signaling
- Immune Response and Inflammation
- Photosynthetic Processes and Mechanisms
- Clostridium difficile and Clostridium perfringens research
- Lipid Membrane Structure and Behavior
- ATP Synthase and ATPases Research
- Autophagy in Disease and Therapy
- NF-κB Signaling Pathways
Vanderbilt University
2009-2025
University of Newcastle Australia
2024
Hunter Medical Research Institute
2024
Vanderbilt Health
2020
Harvard University
2014-2019
Boston University
2019
Vanderbilt University Medical Center
2011
Mitochondrial adenosine triphosphate (ATP) synthase comprises a membrane embedded Fo motor that rotates to drive ATP synthesis in the F1 subunit. We used single-particle cryo-electron microscopy (cryo-EM) obtain structures of full complex lipid bilayer absence or presence inhibitor oligomycin at 3.6- and 3.8-angstrom resolution, respectively. To limit conformational heterogeneity, we locked rotor single conformation by fusing F6 subunit stator with δ rotor. Assembly enzyme F6-δ fusion caused...
Clostridium difficile toxins A and B are members of an important class virulence factors known as large clostridial (LCTs). Toxin action involves four major steps: receptor-mediated endocytosis, translocation a catalytic glucosyltransferase domain across the membrane, release enzymatic moiety by autoproteolytic processing, glucosyltransferase-dependent inactivation Rho family proteins. We have imaged toxin (TcdA) (TcdB) holotoxins negative stain electron microscopy to show that these...
Iron storage proteins are essential for cellular iron homeostasis and redox balance. Ferritin the major units bioavailable forms of iron. Some organisms lack ferritins, it is not known how they store Encapsulins, a class protein-based organelles, have recently been implicated in microbial metabolism. Here, we report structural mechanistic characterization 42 nm two-component encapsulin-based compartment from Quasibacillus thermotolerans. Using cryo-electron microscopy x-ray crystallography,...
How the distinctive lipid composition of mammalian plasma membranes impacts membrane protein structure is largely unexplored, partly because dearth isotropic model systems that contain abundant sphingolipids and cholesterol. This gap addressed by showing sphingomyelin cholesterol-rich (SCOR) mixtures with phosphatidylcholine can be cosolubilized n-dodecyl-β-melibioside to form bicelles. Small-angle X-ray neutron scattering, as well cryo-electron microscopy, demonstrate these assemblies are...
Abstract The B cell survival factor (TNFSF13B/BAFF) is often elevated in autoimmune diseases and targeted the clinic for treatment of systemic lupus erythematosus. BAFF contains a loop region designated flap, which dispensable receptor binding. Here we show that flap has two functions. In addition to facilitating formation highly active 60-mer as shown previously, it also converts binding TNFRSF13C (BAFFR) into signaling event via oligomerization individual BAFF-BAFFR complexes. Binding...
Helicobacter pylori VacA is a pore-forming toxin that causes multiple alterations in human cells and contributes to the pathogenesis of peptic ulcer disease gastric cancer. The secreted by H. as an 88 kDa monomer (p88) consisting two domains (p33 p55). While X-ray crystal structure for p55 exists p88 oligomers have been visualized cryo-electron microscopy, detailed analysis p33 has hindered inability purify this domain active form. In study, we expressed purified recombinant form under...
Essentials•Recombinant factor VIII (rFVIII) Fc fusion protein has a 1.5‐fold longer half‐life than rFVIII.•Five orthogonal methods were used to characterize the structure of rFVIIIFc compared rFVIII.•The C‐terminal does not perturb FVIII in rFVIIIFc.•The and components are flexibly tethered functionally independent.Summary: BackgroundFusion human IgG1 domain C2 B‐domain‐deleted (BDD) (FVIII) results recombinant (rFVIIIFc) protein, which humans.ObjectiveTo assess structural properties by...
Acute myeloid leukemia (AML) is an aggressive and poor-prognosis blood cancer. Despite a low mutation burden compared to other cancers, AML heterogenous identifying robust therapeutic targets has been difficult. Genomic profiling greatly advanced our understanding of AML, revealed for therapy. However, only 50% patients have gene mutations that are currently druggable, relapse rates remain high. The addition proteomic emerging address these challenges.
Abstract The V, D and J segment recombination (V(D)J recombination) is the key event in development maturation of T B lymphocytes, which generates a diverse repertoire cell clones for further selection useful specificities. V(D)J also basis antibody diversity. initiation step carried out by pair lymphocyte specific enzymes, are called recombination-activating gene 1 2 (RAG1 RAG2). RAG1 RAG2 associate with each other two recognition signal sequences (RSS, 12RSS 23RSS) adjacent to coding ends...
Abstract A hallmark of vertebrate immunity is the diverse repertoire antigen-receptor genes that results from combinatorial splicing gene coding segments by V(D)J recombination. The dimeric (RAG1-RAG2)2 recombinase (RAG) recognizes specific recombination signal sequences (RSSs), each containing a heptamer, spacer 12 or 23 base pairs, and nonamer (12-RSS 23-RSS). RAG only combines one 12-RSS 23-RSS, dogma known as 12/23 rule governs fidelity introduces precise breaks at RSS-coding segment...
Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7–August 11, 2011.