A5065413233- Helicobacter pylori-related gastroenterology studies
- Legionella and Acanthamoeba research
- RNA and protein synthesis mechanisms
- Galectins and Cancer Biology
- RNA Research and Splicing
- Veterinary medicine and infectious diseases
- Clostridium difficile and Clostridium perfringens research
- RNA modifications and cancer
- Caveolin-1 and cellular processes
- Toxin Mechanisms and Immunotoxins
- Methane Hydrates and Related Phenomena
- Earthquake Detection and Analysis
- Escherichia coli research studies
- Advanced Electron Microscopy Techniques and Applications
- Bacterial Genetics and Biotechnology
- Vibrio bacteria research studies
- Erythrocyte Function and Pathophysiology
- DNA Repair Mechanisms
- Parasitic Infections and Diagnostics
- Toxoplasma gondii Research Studies
- Freezing and Crystallization Processes
- Ocular Infections and Treatments
- Fungal and yeast genetics research
- Bacterial biofilms and quorum sensing
- Enzyme Structure and Function
University of Michigan
2018-2025
Ann Arbor Center for Independent Living
2024
Washtenaw Community College
2019-2023
Michigan United
2020-2022
Vanderbilt University
2009-2020
Vanderbilt University Medical Center
2011-2018
University of Washington
2011
Harvard University
2006-2007
Membrane-sculpting proteins shape the morphology of cell membranes and facilitate remodeling in response to physiological environmental cues. Complexes monotopic membrane protein caveolin function as essential curvature-generating components caveolae, flask-shaped invaginations that sense respond plasma tension. However, structural basis for caveolin's activity is currently unknown. Here, we show that, using cryo-electron microscopy, human caveolin-1 complex composed 11 protomers organized...
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...
A unique aspect of arrestin-3 is its ability to support both receptor-dependent and receptor-independent signaling. Here, we show that inositol hexakisphosphate (IP6) a non-receptor activator report the structure IP6-activated at 2.4-Å resolution. exhibits an inter-domain twist displaced C-tail, hallmarks active arrestin. IP6 binds arrestin phosphate sensor, stabilized by trimerization. Analysis trimerization surface, which also receptor-binding suggests feature called finger loop as key...
ABSTRACT Bacterial type IV secretion systems (T4SSs) can function to export or import DNA, and deliver effector proteins into a wide range of target cells. Relatively little is known about the structural organization T4SSs that secrete proteins. In this report, we describe isolation analysis membrane-spanning core complex from Helicobacter pylori cag T4SS, which has an important role in pathogenesis gastric cancer. We show contains five H. proteins, CagM, CagT, Cag3, CagX, CagY, each...
Bacterial type IV secretion systems (T4SSs) are molecular machines that can mediate interbacterial DNA transfer through conjugation and delivery of effector molecules into host cells. The Helicobacter pylori Cag T4SS translocates CagA, a bacterial oncoprotein, gastric cells, contributing to cancer pathogenesis. We report the structure membrane-spanning assembly, which we describe as three sub-assemblies: 14-fold symmetric outer membrane core complex (OMCC), 17-fold periplasmic ring (PRC),...
The Rev Response Element (RRE) forms an oligomeric complex with the viral protein to facilitate nuclear export of intron-retaining RNAs during late phase HIV-1 infection. However, our structural understanding this crucial virological process remains limited. In study, we determined several crystal structures intact RRE stem-loop II in two distinct conformations, performed negative-staining electron microscopy and molecular dynamics simulations, revealed that three-way junction RNA exhibits...
Ebolaviruses cause severe disease in humans, and identification of monoclonal antibodies (mAbs) that are effective against multiple ebolaviruses important for therapeutics development. Here we describe a distinct class broadly neutralizing human mAbs with protective capacity three infectious humans: Ebola (EBOV), Sudan (SUDV), Bundibugyo (BDBV) viruses. We isolated from survivors ebolavirus identified potent mAb, EBOV-520, which bound to an epitope the glycoprotein (GP) base region. EBOV-520...
Botulinum neurotoxin (BoNT) is produced by Clostridium botulinum and associates with nontoxic neurotoxin-associated proteins to form high-molecular weight progenitor complexes (PCs). The PCs are required for the oral toxicity of BoNT in context food-borne botulism thought protect from destruction gastrointestinal tract aid absorption gut lumen. PC can differ size protein content depending on C. strain. increases as increases, but molecular architecture these large how they contribute have...
Reconstitution of the PMP22 protein into lipid bilayers results in membrane assemblies that share common features with myelin.
Legionella pneumophila is an opportunistic pathogen that causes the potentially fatal pneumonia Legionnaires' Disease. This infection and subsequent pathology require Dot/Icm Type IV Secretion System (T4SS) to deliver effector proteins into host cells. Compared prototypical T4SSs, assembly much larger, containing ~27 different components including a core complex reported be composed of five proteins: DotC, DotD, DotF, DotG, DotH. Using single particle cryo-electron microscopy (cryo-EM), we...
Schizosaccharomyces pombe (Sp) Cdc5p and its Saccharomyces cerevisiae (Sc) ortholog, Cef1p, are essential components of the spliceosome. In S. cerevisiae, a subcomplex spliceosome that includes Cef1p can be isolated on own; this has been termed nineteen complex (Ntc) because it contains Prp19p. Components Ntc include Snt309p, Syf2p/Ntc31p, Ntc30p/Isy1p, Ntc20p at least six unidentified proteins. We recently identified ∼30 proteins copurified with Cef1p. Previously in purification were called...
Higher-order structures of the microtubule (MT) cytoskeleton are comprised two architectures: bundles and asters. Although both architectures critical for cellular function, molecular pathways that drive aster formation poorly understood. Here, we study by human minus-end-directed kinesin-14 (HSET/KIFC1). We show HSET is incapable forming asters from preformed, nongrowing MTs, but rapidly forms MT in presence soluble (non-MT) tubulin. binds tubulin via its N-terminal tail domain to form...
The pathogenesis of Helicobacter pylori -associated gastric cancer is dependent on delivery CagA into host cells through a type IV secretion system (T4SS). H. Cag T4SS includes large membrane-spanning core complex containing five proteins, organized an outer membrane cap (OMC), periplasmic ring (PR) and stalk. Here, we report cryo-EM reconstructions lacking Cag3 improved map the wild-type complex. We define structures two unique species-specific components (Cag3 CagM) show that structurally...
Abstract Lecithin:cholesterol acyltransferase (LCAT) catalyzes a critical step of reverse cholesterol transport by esterifying in high density lipoprotein (HDL) particles. LCAT is activated apolipoprotein A-I (ApoA-I), which forms double belt around HDL, however the manner engages its lipidic substrates and ApoA-I HDL poorly understood. Here, we used negative stain electron microscopy, crosslinking, hydrogen-deuterium exchange studies to refine molecular details LCAT–HDL complex. Our data...
Significance Respiratory syncytial virus is a highly contagious human pathogen, infecting the majority of infants before age 2 y, and leading cause viral bronchiolitis pneumonia in children. An approved prophylactic humanized mouse monoclonal antibody, palivizumab, currently standard-of-care treatment for immunocompromised individuals, competition with palivizumab has been proposed as basis measuring effective immune responses vaccine trials. Using combination X-ray crystallography,...