A5054738052- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Escherichia coli research studies
- Genomics and Phylogenetic Studies
- Enzyme Structure and Function
- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Protein Structure and Dynamics
- Antibiotic Resistance in Bacteria
- Pharmacological Effects of Natural Compounds
- Tracheal and airway disorders
- Cell Adhesion Molecules Research
- Neurotransmitter Receptor Influence on Behavior
- Berberine and alkaloids research
- Congenital Diaphragmatic Hernia Studies
- Protease and Inhibitor Mechanisms
- Protein purification and stability
- Attention Deficit Hyperactivity Disorder
- Wastewater Treatment and Nitrogen Removal
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Behavioral and Psychological Studies
- Mycobacterium research and diagnosis
- Diphtheria, Corynebacterium, and Tetanus
- Plant-based Medicinal Research
Harvard University
1985-2025
Howard Hughes Medical Institute
2024-2025
Princeton University
2018-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2019
Significance The spread of multidrug-resistant infections demands antibiotic development. Although new antibiotics targeting gram-positive bacteria have been developed, it has more than 50 y since a class gram-negative approved for clinical use. strong outer membrane permeability barrier makes difficult compounds to reach intracellular targets, contributing greatly the lack this microbes. Here, we describe compound, MRL-494, that inhibits assembly proteins into by an essential member...
Abstract Protein turnover is critical for proteostasis, but quantification challenging, and even in well-studied E. coli , proteome-wide measurements remain scarce. Here, we quantify the rates of ~3200 proteins under 13 conditions by combining heavy isotope labeling with complement reporter ion find that cytoplasmic are recycled when nitrogen limited. We use knockout experiments to assign substrates known ATP-dependent proteases. Surprisingly, none these proteases responsible observed...
The β-barrel assembly machine (Bam) complex folds and inserts integral membrane proteins into the outer of Gram-negative bacteria. two essential components complex, BamA BamD, both interact with substrates, but how coordinate each other during is not clear. To elucidate aspects this process we slowed an substrate Bam LptD, by changing a conserved residue near C terminus. This defective recruited to via BamD unable integrate efficiently. Changes in extracellular loops partially restore...
The mycobacterial cell envelope plays both infectious and protective roles. Understanding its structure is crucial for unlocking the molecular basis underlying these functions. Studying glycans, primary components of envelope, challenging due to their limited native functional handles chemoselective modification. New labeling methods exploit biorthogonal chemistry, using small molecule mimics that intercept cellular metabolism or late-stage glycan biosynthesis. However, strategies can have...
Protein assembly into lipid bilayers is an essential process that ensures the viability of diverse organisms. In Gram-negative bacteria, heteropentomeric β-barrel machine (Bam) folds and inserts proteins outer membrane. Due to its essentiality, membrane protein (OMP) by Bam complex attractive target for antibiotic development. Here, we show conditional lethal phenotype a mutant lacking two three nonessential lipoproteins, BamB BamE, caused jamming stripped-down normally surface-exposed...
Significance The assembly of β-barrel outer membrane proteins (OMPs) is broadly conserved in diderm bacteria as well mitochondria and chloroplasts. machine (BAM), which assembles OMPs into the gram-negative microbes, contains two essential proteins, BamA BamD. Here we identify a genetic background BamD nonessential, indicating that does not function OMP catalysis, but rather plays regulatory role assembly. complexes assemble chloroplasts mitochondria, likely because these organelles, unlike...
ABSTRACT The heteropentomeric β-barrel assembly machine (BAM complex) is responsible for folding and inserting a diverse array of outer membrane proteins (OMPs) into the (OM) Gram-negative bacteria. BAM complex contains two essential proteins, OMP BamA lipoprotein BamD, whereas auxiliary lipoproteins BamBCE are individually nonessential. Here, we identify characterize three bamA mutations, E-to-K change at position 470 ( E470K ), A-to-P 496 A496P A-to-S 499 A499S that suppress otherwise...
Significance The bacterial cell envelope is the frontline defense against host immune factors and antibiotics. regulator of capsule synthesis (Rcs) a complex signaling pathway that maintains homeostasis this essential organelle. Several hypotheses for how sensory component RcsF activates in response to stress were proposed but could not be directly tested because proper assembly into with outer membrane proteins (OMPs) depends on β-barrel machine (Bam). We used an extensive genetic analysis...
Protein lipidation dynamically controls protein localization and function within cellular membranes. A unique form of
Summary Protein turnover is critical for proteostasis, but quantification challenging, and even in well-studied E. coli , proteome-wide measurements remain scarce. Here, we quantify the degradation rates of ∼3.2k proteins under 12 conditions by combining heavy isotope labeling with complement reporter ion find that cytoplasmic are recycled when nitrogen limited. We use knockout experiments to assign substrates known ATP-dependent proteases. Surprisingly, none these proteases responsible...
The cell envelope fortifies bacterial cells against antibiotics and other insults. Species in the Mycobacteriales order have a complex that includes an outer layer of mycolic acids called mycomembrane (MM) wall composed peptidoglycan arabinogalactan. This architecture is unique among bacteria contributes significantly to virulence pathogenic like Mycobacterium tuberculosis. Characterization pathways govern biogenesis these organisms therefore critical understanding their biology for...
The Gram-negative outer membrane (OM) is a selectively permeable asymmetric bilayer that allows vital nutrients to diffuse into the cell but prevents toxins and hydrophobic molecules from entering. Functionally structurally diverse β-barrel proteins (OMPs) build maintain permeability barrier, making assembly of OMPs crucial for viability. In this work, we characterize an assembly-defective mutant maltoporin LamB, LamB
The cell envelope fortifies bacterial cells against antibiotics and other insults. Species in the Mycobacteriales order have a complex that includes an outer layer of mycolic acids called mycomembrane (MM) wall composed peptidoglycan arabinogalactan. This architecture is unique among bacteria contributes significantly to virulence pathogenic like Mycobacterium tuberculosis . Characterization pathways govern biogenesis these organisms therefore critical understanding their biology for...