Joseph A. Loo
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View article: Allosteric Modulation of Pathological Ataxin‐3 Aggregation: A Path to Spinocerebellar Ataxia Type‐3 Therapies
Allosteric Modulation of Pathological Ataxin‐3 Aggregation: A Path to Spinocerebellar Ataxia Type‐3 Therapies Open
Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disorder caused by the expansion of a polyglutamine (polyQ) repeat in ataxin‐3 (Atx3) for which no disease‐modifying therapies are available. The presence of protein inclusio…
View article: Structural basis for L-isoaspartyl-containing protein recognition by the human PCMTD1 cullin-RING E3 ubiquitin ligase
Structural basis for L-isoaspartyl-containing protein recognition by the human PCMTD1 cullin-RING E3 ubiquitin ligase Open
A major type of spontaneous protein damage that accumulates with age is the formation of kinked polypeptide chains with L-isoaspartyl residues. Mitigating this damage is necessary for maintaining proteome stability and prolonging organisma…
View article: Leveraging bioorthogonal conjugation for alpha synuclein fibril surveillance
Leveraging bioorthogonal conjugation for alpha synuclein fibril surveillance Open
Alpha synuclein (α-syn) amyloid fibrils are associated with various neurodegenerative diseases. To better understand the molecular and cellular basis for α-syn fibril persistence and spread, we implemented a fluorophore labeling strategy t…
View article: GFAP Degradation in TBI: Linking Novel Modified Products to Astrocyte Pathology and Patient Outcome
GFAP Degradation in TBI: Linking Novel Modified Products to Astrocyte Pathology and Patient Outcome Open
Glial fibrillary acidic protein (GFAP) is an important clinical biomarker of traumatic brain injury (TBI), yet understanding the nature, timing, and impact of its degraded and modified products is needed for clinical utility. We report dis…
View article: Combining MicroED and native mass spectrometry for structural discovery of enzyme–small molecule complexes
Combining MicroED and native mass spectrometry for structural discovery of enzyme–small molecule complexes Open
With the goal of accelerating the discovery of small molecule–protein complexes, we leverage fast, low-dose, event-based electron counting microcrystal electron diffraction (MicroED) data collection and native mass spectrometry. This appro…
View article: An Organometallic Chemistry Approach to Peptide Tricycles
An Organometallic Chemistry Approach to Peptide Tricycles Open
Herein, we demonstrate how Au(III) organometallic chemistry offers the potential to streamline the generation of constrained peptide tricycles. By leveraging the chemoselectivity and ultrafast kinetics of tetrametallic Au(III)-based aryl r…
View article: Structural basis for L-isoaspartyl-containing protein recognition by the PCMTD1 cullin-RING E3 ubiquitin ligase
Structural basis for L-isoaspartyl-containing protein recognition by the PCMTD1 cullin-RING E3 ubiquitin ligase Open
Summary A major type of spontaneous protein damage that accumulates with age is the formation of kinked polypeptide chains with L-isoaspartyl residues. Mitigating this damage is necessary for maintaining proteome stability and prolonging o…
View article: Combining MicroED and native mass spectrometry for structural discovery of enzyme-biosynthetic inhibitor complexes
Combining MicroED and native mass spectrometry for structural discovery of enzyme-biosynthetic inhibitor complexes Open
With the goal of accelerating the discovery of small molecule-protein complexes, we leverage fast, low-dose, event based electron counting microcrystal electron diffraction (MicroED) data collection and native mass spectrometry. This appro…
View article: Allosteric Modulation of Pathological Ataxin-3 Aggregation: A Path to Spinocerebellar Ataxia Type-3 Therapies
Allosteric Modulation of Pathological Ataxin-3 Aggregation: A Path to Spinocerebellar Ataxia Type-3 Therapies Open
Spinocerebellar ataxia type 3 (SCA3) is a rare inherited neurodegenerative disease caused by the expansion of a polyglutamine repeat in the protease ataxin-3 (Atx3). Despite extensive knowledge of the downstream pathophysiology, no disease…
View article: The Exoproteome and Surfaceome of Toxigenic <i>Corynebacterium diphtheriae</i> 1737 and Its Response to Iron Restriction and Growth on Human Hemoglobin
The Exoproteome and Surfaceome of Toxigenic <i>Corynebacterium diphtheriae</i> 1737 and Its Response to Iron Restriction and Growth on Human Hemoglobin Open
Toxin-producing Corynebacterium diphtheriae strains are the etiological agents of the severe upper respiratory disease, diphtheria. A global phylogenetic analysis revealed that biotype gravis is particularly lethal as it produces diphtheri…
View article: Composition and in situ structure of the <i>Methanospirillum hungatei</i> cell envelope and surface layer
Composition and in situ structure of the <i>Methanospirillum hungatei</i> cell envelope and surface layer Open
Archaea share genomic similarities with Eukarya and cellular architectural similarities with Bacteria, though archaeal and bacterial surface layers (S-layers) differ. Using cellular cryo–electron tomography, we visualized the S-layer latti…
View article: Top-down proteomics
Top-down proteomics Open
Proteoforms, which arise from post-translational modifications, genetic polymorphisms and RNA splice variants, play a pivotal role as drivers in biology. Understanding proteoforms is essential to unravel the intricacies of biological syste…
View article: The exoproteome and surfaceome of toxigenic<i>Corynebacterium diphtheriae</i>1737 and its response to iron-restriction and growth on human hemoglobin
The exoproteome and surfaceome of toxigenic<i>Corynebacterium diphtheriae</i>1737 and its response to iron-restriction and growth on human hemoglobin Open
Toxin-producing Corynebacterium diphtheriae strains are the etiological agent of the severe upper respiratory disease, diphtheria. A global phylogenetic analysis revealed that biotype gravis is particularly lethal as it produces diphtheria…
View article: D-peptide-magnetic nanoparticles fragment tau fibrils and rescue behavioral deficits in a mouse model of Alzheimer’s disease
D-peptide-magnetic nanoparticles fragment tau fibrils and rescue behavioral deficits in a mouse model of Alzheimer’s disease Open
Amyloid fibrils of tau are increasingly accepted as a cause of neuronal death and brain atrophy in Alzheimer’s disease (AD). Diminishing tau aggregation is a promising strategy in the search for efficacious AD therapeutics. Previously, our…
View article: Ultrafast Au(III)-Mediated Arylation of Cysteine
Ultrafast Au(III)-Mediated Arylation of Cysteine Open
Through mechanistic work and rational design, we have developed the fastest organometallic abiotic Cys bioconjugation. As a result, the developed organometallic Au(III) bioconjugation reagents enable selective labeling of Cys moieties down…
View article: Insight into the autoproteolysis mechanism of the RsgI9 anti‐σ factor from <i>Clostridium thermocellum</i>
Insight into the autoproteolysis mechanism of the RsgI9 anti‐σ factor from <i>Clostridium thermocellum</i> Open
Clostridium thermocellum is a potential microbial platform to convert abundant plant biomass to biofuels and other renewable chemicals. It efficiently degrades lignocellulosic biomass using a surface displayed cellulosome, a megadalton siz…
View article: Internal Fragments Enhance Middle-Down Mass Spectrometry Structural Characterization of Monoclonal Antibodies and Antibody-Drug Conjugates
Internal Fragments Enhance Middle-Down Mass Spectrometry Structural Characterization of Monoclonal Antibodies and Antibody-Drug Conjugates Open
Monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) are important large biotherapeutics (∼150 kDa) and high structural complexity that require extensive sequence and structure characterization. Middle-down mass spectrometry (M…
View article: Detection of Lipid-Bound Bacteriorhodopsin Trimer Complex Directly from Purple Membrane by Native Mass Spectrometry
Detection of Lipid-Bound Bacteriorhodopsin Trimer Complex Directly from Purple Membrane by Native Mass Spectrometry Open
Native mass spectrometry (MS) was used to detect the membrane protein, bacteriorhodopsin (bR), in its 27 kDa monomeric form and trimeric assemblies directly from lipid-containing purple membranes (PMs) from the halophilic archaeon, Halobac…
View article: Characterization of Molecular Tweezer Binding on α-Synuclein with Native Top-Down Mass Spectrometry and Ion Mobility-Mass Spectrometry Reveals a Mechanism for Aggregation Inhibition
Characterization of Molecular Tweezer Binding on α-Synuclein with Native Top-Down Mass Spectrometry and Ion Mobility-Mass Spectrometry Reveals a Mechanism for Aggregation Inhibition Open
Parkinson's disease, a neurodegenerative disease that affects 15 million people worldwide, is characterized by deposition of α-synuclein into Lewy Bodies in brain neurons. Although this disease is prevalent worldwide, a therapy or cure has…
View article: Mapping Molecular Interaction Interface Between Diaphanous Formin-2 and Neuron-Specific Drebrin A
Mapping Molecular Interaction Interface Between Diaphanous Formin-2 and Neuron-Specific Drebrin A Open
Actin cytoskeleton is critical for neuronal shape and function. Drebrin and formins are key regulators of neuronal actin networks. Neuron-specific drebrin A is highly enriched in dendritic spines (postsynaptic terminals) of mature excitato…
View article: Structure-based design of nanobodies that inhibit seeding of Alzheimer’s patient–extracted tau fibrils
Structure-based design of nanobodies that inhibit seeding of Alzheimer’s patient–extracted tau fibrils Open
Despite much effort, antibody therapies for Alzheimer’s disease (AD) have shown limited efficacy. Challenges to the rational design of effective antibodies include the difficulty of achieving specific affinity to critical targets, poor exp…
View article: Top-down mass spectrometry of native proteoforms and their complexes: A community study
Top-down mass spectrometry of native proteoforms and their complexes: A community study Open
The combination of native electrospray ionisation with top-down fragmentation in mass spectrometry allows simultaneous determination of the stoichiometry of noncovalent complexes and identification of their component proteoforms and co-fac…
View article: Added Value of Internal Fragments for Top-Down Mass Spectrometry of Intact Monoclonal Antibodies and Antibody–Drug Conjugates
Added Value of Internal Fragments for Top-Down Mass Spectrometry of Intact Monoclonal Antibodies and Antibody–Drug Conjugates Open
Monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) are two of the most important therapeutic drug classes that require extensive characterization, whereas their large size and structural complexity make them challenging to ch…
View article: The basal and major pilins in the <i>Corynebacterium diphtheriae</i> <scp>SpaA</scp> pilus adopt similar structures that competitively react with the pilin polymerase
The basal and major pilins in the <i>Corynebacterium diphtheriae</i> <span>SpaA</span> pilus adopt similar structures that competitively react with the pilin polymerase Open
Many species of pathogenic gram‐positive bacteria display covalently crosslinked protein polymers (called pili or fimbriae) that mediate microbial adhesion to host tissues. These structures are assembled by pilus‐specific sortase enzymes t…
View article: mTORC2 interactome and localization determine aggressiveness of high-grade glioma cells through association with gelsolin
mTORC2 interactome and localization determine aggressiveness of high-grade glioma cells through association with gelsolin Open
mTOR complex 2 (mTORC2) has been implicated as a key regulator of glioblastoma cell migration. However, the roles of mTORC2 in the migrational control process have not been entirely elucidated. Here, we elaborate that active mTORC2 is cruc…
View article: Supplementary Table 2 from Salivary Proteomics for Oral Cancer Biomarker Discovery
Supplementary Table 2 from Salivary Proteomics for Oral Cancer Biomarker Discovery Open
Supplementary Table 2 from Salivary Proteomics for Oral Cancer Biomarker Discovery