Structural Proteomics

Autism spectrum disorder (ASD) is a developmental disorder with a rising prevalence and unknown etiology presenting with deficits in cognition and abnormal behavior. We hypothesized that the investigation of the synaptic component of prefrontal cortex may provide proteomic signatures that may identify the biological underpinnings of cognitive deficits in childhood ASD. Subcellular fractions of synaptosomes from prefrontal cortices of age-, brain area-, and postmortem-interval-matched samples from children and adults with idiopathic ASD vs...

Here, we investigated the mechanisms by which aging-related reductions of the levels of Numb in skeletal muscle fibers contribute to loss of muscle strength and power, two critical features of sarcopenia. Numb is an adaptor protein best known for its critical roles in development, including asymmetric cell division, cell-type specification, and termination of intracellular signaling. Numb expression is reduced in old humans and mice. We previously showed that, in mouse skeletal muscle fibers, Numb is localized to sarcomeres where it is concentrated near triads; conditional inactivation of Numb and a closely related protein Numb -like ( Numbl ) in mouse myofibers caused weakness, disorganization of sarcomeres, and smaller mitochondria with impaired function...

Ribosomes are universally conserved cellular machines that catalyze protein biosynthesis. The active sites underly immense evolutionary conservation resulting in virtually identical core structures of ribosomes in all domains of life including organellar ribosomes. However, more peripheral structures of cytosolic ribosomes changed during evolution accommodating new functions and regulatory options. The expansion occurred at the riboprotein level, including more and larger ribosomal proteins and at the RNA level increasing the length of ribosomal RNA...

BACKGROUND: N6-adenosine methylation (m6A) is a prevalent RNA modification associated with heart failure, alongside aberrant miRNA expression. Despite indications of miRNAs regulating m6A modification, their specific influence on m6A in heart failure remains unclear. METHODS: The initial analysis utilized transcriptome and methylation sequencing data from GSE131296 in mice to identify key m6A methylation enzymes in heart failure and construct an associated network...

Hair is an advantageous biological sample due to its recordable, collectable, and storable nature. Hair's primary components are keratin and keratin-associated proteins. Owing to its abundance of cystine, keratin possesses impressive mechanical strength and chemical stability, formed by creating disulfide bonds as crosslinks within the protein peptide chain. Furthermore, keratin is cross-linked with keratin-associated proteins to create a complex network structure that provides the hair with strength and rigidity...

Spatial segmentation is an essential processing method for image analysis aiming to identify the characteristic suborgans or microregions from mass spectrometry imaging (MSI) data, which is critical for understanding the spatial heterogeneity of biological information and function and the underlying molecular signatures. Due to the intrinsic characteristics of MSI data including spectral nonlinearity, high-dimensionality, and large data size, the common segmentation methods lack the capability for capturing the accurate microregions associated with biological functions...

Recent advances in high-throughput proteomic profiling technologies have facilitated the precise quantification of numerous proteins across multiple specimens concurrently. Researchers have the opportunity to comprehensively analyze the molecular signatures in plentiful medical specimens or disease pattern cell lines. Along with advances in data analysis and integration, proteomics data could be efficiently consolidated and employed to recognize precise elementary molecular mechanisms and decode individual biomarkers, guiding the precision treatment of tumors...

Magnesium (Mg)-based implants have emerged as a promising alternative for orthopedic applications, owing to their bioactive properties and biodegradability. As the implants degrade, Mg2+ ions are released, influencing all surrounding cell types, especially mesenchymal stem cells (MSCs). MSCs are vital for bone tissue regeneration, therefore, it is essential to understand their molecular response to Mg2+ ions in order to maximize the potential of Mg-based biomaterials. In this study, we conducted a gene regulatory network (GRN) analysis to examine the molecular responses of MSCs to Mg2+ ions...

Phosphorylation plays a crucial role in the regulation of many fundamental cellular processes. Phosphorylation levels are increased in many cancer cells where they may promote changes in mitochondrial homeostasis. Proteomic studies on various types of cancer identified 17 phosphorylation sites within the human ATP-dependent protease Lon, which degrades misfolded, unassembled and oxidatively damaged proteins in mitochondria. Most of these sites were found in Lon's N-terminal (NTD) and ATPase domains, though little is known about the effects on their function...

As the demographic structure shifts towards an aging society, strategies aimed at slowing down or reversing the aging process become increasingly essential. Aging is a major predisposing factor for many chronic diseases in humans. The hematopoietic system, comprising blood cells and their associated bone marrow microenvironment, intricately participates in hematopoiesis, coagulation, immune regulation and other physiological phenomena. The aging process triggers various alterations within the hematopoietic system, serving as a spectrum of risk factors for hematopoietic disorders, including clonal hematopoiesis, immune senescence, myeloproliferative neoplasms and leukemia...

The correct characterization and identification of different kinds of proteins is crucial for the survival and development of living organisms, and proteomics research promotes the analysis and understanding of future genome functions. Nanopore technique has been proved to accurately identify individual nucleotides. However, accurate and rapid protein sequencing is difficult due to the variability of protein structures that contains more than 20 amino acids, and it remains very challenging especially for uncharged peptides as they can not be electrophoretically driven through the nanopore...

During germination plants rely entirely on their seed storage compounds to provide energy and precursors for the synthesis of macromolecular structures until the seedling has emerged from the soil and photosynthesis can be established. Lupin seeds use proteins as their major storage compounds, accounting for up to 40% of the seed dry weight. Lupins are therefore a valuable complement to soy as a source of plant protein for human and animal nutrition. The aim of this study was to elucidate how storage protein metabolism is coordinated with other metabolic processes to meet the requirements of the growing seedling...

Protein-protein interactions (PPIs) play a critical role in cellular signaling and represent interesting targets for therapeutic intervention. 14-3-3 proteins integrate many signaling targets via PPIs and are frequently implicated in disease, making them intriguing drug targets. Here, we review the recent advances in the 14-3-3 field. It will discuss the roles 14-3-3 proteins play within the cell, elucidation of their expansive interactome, and the complex mechanisms that underpin their function. In addition, the review will discuss significant advances in the development of molecular glues that target 14-3-3 PPIs...

Tyrosine phosphorylation is one of the most important posttranslational modifications in bacteria, linked to regulating growth, migration, virulence, secondary metabolites, biofilm formation, and capsule production. Only two tyrosine kinases (yccC (etk) and wzc) have been identified in Escherichia coli . The investigation by similarity has not revealed any novel BY-kinases in silico so far, most probably due to their sequence and structural variability. Here we developed a reverse-phase protein array from 4126 overexpressed E...

OBJECTIVE: Analyze the molecular mimicry between Plasmodium spp. and autoantigens associated with GBS, identifying possible antigenic epitopes. METHODS: PSI-Blast, Praline, Emboss, Protein Data Bank, Swiss Model Server, AlphaFold 2, Ellipro and PyMol 2.3 were used to search for homologies, perform alignments, obtain protein structures, and predict epitopes. RESULTS: 17 autoantigens and seven immunological targets of the peripheral nervous system were included, identifying 72 possible epitopes associated with GBS...

Biofilms, which consist of microorganisms enclosed in an extracellular polymeric material (EPS), hold immense importance in the fields of environmental research, industry, and medicine. They play a significant role in ecosystem dynamics and stability, but they also pose issues such as biofouling, corrosion, and pollution. Biofilms in medical environments are linked to persistent infections and elevated healthcare expenses. The EPS matrix plays a crucial role in maintaining the structural integrity and antibiotic resistance of these structures...

Discovering macromolecules and understanding the associated mechanisms involved in underwater adhesion are essential for both studying the fundamental ecology of benthos in aquatic ecosystems and developing biomimetic adhesive materials in industries. Here, we employed quantitative proteomics to assess protein expression variations during the development of the distinct adhesive structure - stolon in the model fouling ascidian, Ciona robusta. We found 16 adhesive protein candidates with increased expression in the stolon, with ascidian adhesive protein 1 (AAP1) being particularly rich in adhesion-related signal peptides, amino acids, and functional domains...

OBJECTIVE: During physical activities, chondrocytes experience coupled stimulation of hydrostatic pressure (HP) and a transient increase in temperature (T), with the latter varying within a physiological range from 32.5 °C to 38.7 °C. Previous short-term in vitro studies have demonstrated that the combined HP-T stimuli more significantly enhance chondroinduction and chondroprotection of chondrocytes than isolated applications. Interestingly, this combined benefit is associated with a corresponding increase in HSP70 levels when HP and T are combined...

Malaria vaccine development is hampered by extensive antigenic variation and complex life stages of Plasmodium species. Vaccine development has focused on a small number of antigens, many of which were identified without utilizing systematic genome-level approaches. In this study, we implement a machine learning-based reverse vaccinology approach to predict potential new malaria vaccine candidate antigens. We assemble and analyze P. falciparum proteomic, structural, functional, immunological, genomic, and transcriptomic data, and use positive-unlabeled learning to predict potential antigens based on the properties of known antigens and remaining proteins...

De novo protein folding into a native three-dimensional structure is indispensable for biological function, is instructed by its amino acid sequence, and occurs along a vectorial trajectory. The human proteome contains thousands of membrane-spanning proteins, whose biosynthesis begins on endoplasmic reticulum-associated ribosomes. Nearly half of all membrane proteins traverse the membrane more than once, including therapeutically important protein families such as solute carriers, G-protein-coupled receptors, and ABC transporters...