A5036129613- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Escherichia coli research studies
- Bacteriophages and microbial interactions
- Ubiquitin and proteasome pathways
- T-cell and B-cell Immunology
- Viral gastroenteritis research and epidemiology
- Erythrocyte Function and Pathophysiology
- Immune Cell Function and Interaction
- Porphyrin Metabolism and Disorders
- RNA and protein synthesis mechanisms
- Neonatal and Maternal Infections
- Metabolism and Genetic Disorders
- Toxin Mechanisms and Immunotoxins
- Clostridium difficile and Clostridium perfringens research
- Aquaculture disease management and microbiota
- Endoplasmic Reticulum Stress and Disease
- SARS-CoV-2 and COVID-19 Research
- Blood groups and transfusion
- Peptidase Inhibition and Analysis
- Influenza Virus Research Studies
- Neuropeptides and Animal Physiology
- Streptococcal Infections and Treatments
- Respiratory viral infections research
Illinois College
2022-2024
University of Illinois Urbana-Champaign
2019-2024
California Institute of Technology
2015-2018
University of Utah
2007-2012
Since the COVID-19 pandemic onset, antibody response to SARS-CoV-2 has been extensively characterized. Antibodies receptor binding domain (RBD) on spike protein are frequently encoded by IGHV3-53/3-66 with a short complementarity-determining region (CDR) H3. Germline-encoded sequence motifs in heavy chain CDRs H1 and H2 have major function, but whether any common present CDR H3, which is often critical for specificity, not clear. Here, we identify two public clonotypes of RBD antibodies...
As a first-line vertebrate immune defense, the polymeric immunoglobulin receptor (pIgR) transports IgA and IgM across epithelia to mucosal secretions, where cleaved ectodomain (secretory component; SC) becomes component of secretory antibodies, or when unliganded, binds excludes bacteria. Here we report 2.6Å crystal structure unliganded human SC (hSC) comparisons with 1.7Å teleost fish (tSC), an early pIgR ancestor. The hSC comprises five immunoglobulin-like domains (D1-D5) arranged as...
HIV-1 Envelope (Env) mediates viral-host membrane fusion after binding host-receptor CD4 and coreceptor. Soluble envelopes (SOSIPs), designed to mimic prefusion conformational states of virion-bound envelopes, are proposed immunogens for eliciting neutralizing antibodies, yet only static structures available. To evaluate landscapes ligand-free, CD4-bound, inhibitor-bound, antibody-bound SOSIPs, we measured inter-subunit distances throughout spin-labeled SOSIPs using double electron-electron...
Secretory (S) Immunoglobulin (Ig) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA a polymeric typically containing two copies of IgA that assemble with one joining-chain (JC) to form dimeric (d) bound by Ig-receptor ectodomain, called secretory component (SC). Here, we report cryo-electron microscopy structures murine dIgA. Structures reveal IgAs conjoined through four heavy-chain tailpieces JC together β-sandwich-like fold. The are bent tilted...
The 20S proteasome is an essential, 28-subunit protease that sequesters proteolytic sites within a central chamber, thereby repressing substrate degradation until activators open the entrance/exit gate. Two established activators, Blm10 and PAN/19S, induce gate opening by binding to pockets between α-subunits using C-terminal HbYX (hydrophobic-tyrosine-any residue) motifs. Equivalent motifs have been identified in Pba1 Pba2, which function assembly. Here, we demonstrate Pba1-Pba2 proteins...
Proteasome activity is regulated by sequestration of its proteolytic centers in a barrel-shaped structure that limits substrate access. Substrates enter the proteasome means activator complexes bind to end rings alpha subunits and induce opening an axial entrance/exit pore. The PA26 binds pocket on surface using main chain contacts C-terminal residues uses internal activation loop trigger gate repositioning Pro-17 reverse turn. Subunits unrelated PAN/19S activators with their C termini same...
Abstract The polymeric Ig receptor (pIgR) transports Abs across epithelia to the mucosa, where proteolytic cleavage releases ectodomain (secretory component [SC]) as an integral of secretory Abs, or unliganded protein that can mediate interactions with bacteria. SC is conserved among vertebrates, but domain organization variable: mammalian has five domains (D1-D5), whereas avian, amphibian, and reptilian lack D2 domain, fish lacks D2-D4. In this study, we used double electron–electron...
Polymeric (p) immunoglobulins (Igs) serve broad functions during vertebrate immune responses. Typically, pIgs contain between two and six Ig monomers, each with antigen binding fragments one fragment crystallization (Fc). In addition, many assemble a joining-chain (JC); however, the number of monomers potential to include JC vary species heavy chain class. Here, we report cryo-electron microscopy structure IgM from teleost (t) species, which does not encode JC. The reveals four tIgM Fcs...
Abstract Since the COVID-19 pandemic onset, antibody response to SARS-CoV-2 has been extensively characterized. Antibodies receptor binding domain (RBD) on spike protein are frequently encoded by IGHV3-53/3-66 with a short CDR H3. Germline-encoded sequence motifs in CDRs H1 and H2 play major role, but whether any common present H3, which is often critical for specificity, have not elucidated. Here, we identify two public clonotypes of RBD antibodies 9-residue H3 that pair different light...
Influenza A virus (IAV) is a respiratory pathogen that remains significant source of morbidity and mortality. Escape from host immunity or emergence into new species often requires mutations modulate the functional activities viral glycoproteins hemagglutinin (HA) neuraminidase (NA), which are responsible for attachment to release cells, respectively.
Abstract Immunoglobulin (Ig) A functions as monomeric IgA in the serum and Secretory (S) mucosal secretions. Host Fc receptors (FcαRs), including human FcαR1/CD89, mediate effector functions; however, pathogen Streptococcus pyogenes has evolved surface-protein virulence factors, M4, that also engage CD89-binding site on IgA. Despite mucosa serving a reservoir for pathogens, SIgA interactions with CD89 M4 remain poorly understood. Here we report cryo-EM structures of M4-SIgA CD89-SIgA...
Secretory (S) IgA is the predominant mucosal Ab that protects host epithelial barriers and promotes microbial homeostasis. SIgA production occurs when plasma cells assemble two copies of monomeric one joining chain (JC) to form dimeric (d) IgA, which bound by polymeric Ig receptor (pIgR) on basolateral surface transcytosed apical surface. There, pIgR proteolytically cleaved, releasing SIgA, a complex dIgA ectodomain, called secretory component (SC). The pIgR's five Ig-like domains (D1-D5)...
Abstract Secretory (S) Immunoglobulin (I) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA a polymeric typically containing two copies of IgA that assemble with one joining-chain (JC) to form dimeric (d) bound by Ig-receptor ectodomain, called secretory component (SC). Here we report cryo-electron microscopy structures murine dIgA. Structures reveal IgAs conjoined through four heavy-chain tailpieces JC together β-sandwich-like fold. The are bent...
Polymeric (p) immunoglobulins (Igs) serve broad functions during vertebrate immune responses. Typically, pIgs contain between two and six Ig monomers, each with antigen binding fragments one fragment crystallization (Fc). In addition, many assemble a joining-chain (JC); however, the number of monomers potential to include JC varies species heavy chain class. Here, we report cryo-electron microscopy structure IgM from teleost (t) species, which does not encode JC. The revealed four tIgM Fcs...
ABSTRACT Immunoglobulin (Ig) A functions as monomeric IgA in the serum and Secretory (S) mucosal secretions. Host Fc receptors (FcαRs), including human FcαR1/CD89, mediate effector functions; however pathogen Streptococcus pyogenes has evolved surface-protein virulence factors, M4, that also engage CD89 binding site on IgA. Despite mucosa serving a reservoir for pathogens, SIgA interactions with M4 remain poorly understood. Here we report cryo-EM structures of M4-SIgA CD89-SIgA complexes,...
Abstract Secreted immunoglobulins, predominantly SIgA, influence the colonization and pathogenicity of mucosal bacteria. While part this effect can be explained by SIgA-mediated bacterial aggregation, we have an incomplete picture how SIgA binding influences cells independently aggregation. Here show that akin to microscale crosslinking cells, targeting Salmonella Typhimurium O-antigen extensively crosslinks O-antigens on surface individual at nanoscale. This results in essentially...
Immunoglobulin A (IgA) is the most abundant antibody isotype produced across mammals and plays a specialized role in mucosal homeostasis(1). Constantly secreted into lumen of intestine, IgA binds commensal microbiota to regulate their colonization function(2,3) with unclear implications for health. deficiency common humans but difficult study due its complex aetiology comorbidities(4-8). Using genetically environmentally controlled mice, here we show that IgA-deficient animals have increased...
Introductory paragraph The ability of gut bacterial pathogens to escape immunity by antigenic variation, particularly via changes surface-exposed antigens, is a major barrier immune clearance 1 . However, not all variants are equally fit in environments 2, 3 It should therefore be possible exploit such mechanisms direct an evolutionary trade-off. Here we demonstrated this phenomenon using Salmonella enterica subspecies serovar Typhimurium ( S. Tm). A dominant surface antigen Tm its...