CLPB

ECF (extracytoplasmic function) σ factors, members of the σ70 -family, are the largest class of alternative σ factors which are stimulated in the presence of specific signals and direct RNA polymerase to transcribe a defined subset of genes. Thanks to them, bacterial pathogens can effectively reprogram their gene expression and, consequently, survive in the host and establish infection in a relatively short time. The number of ECF σ factors encoded within bacterial genomes is different depending on a given species and it reflects the likelihood that these bacteria will encounter harsh environmental conditions...

Heat stress can cause cell death by triggering the aggregation of essential proteins. In bacteria, aggregated proteins are rescued by the canonical Hsp70/AAA+ (ClpB) bi-chaperone disaggregase. Man-made, severe stress conditions applied during, e.g., food processing represent a novel threat for bacteria by exceeding the capacity of the Hsp70/ClpB system. Here, we report on the potent autonomous AAA+ disaggregase ClpL from Listeria monocytogenes that provides enhanced heat resistance to the food-borne pathogen enabling persistence in adverse environments...

The congenital neutropenia syndromes are rare haematological conditions defined by impaired myeloid precursor differentiation or function. Patients are prone to severe infections with high mortality rates in early life. While some patients benefit from granulocyte colony-stimulating factor treatment, they may still face an increased risk of bone marrow failure, myelodysplastic syndrome and acute leukaemia. Accurate diagnosis is crucial for improved outcomes; however, diagnosis depends on familiarity with a heterogeneous group of rare disorders that remain incompletely characterised...

Mycobacterium tuberculosis (Mtb) caseinolytic protease B (ClpB) is a chaperone possessing a unique ability to resolubilize the aggregated proteins in vivo. ClpB has been shown to be important for the survival of Mtb within the host. Thus, it appears to be a promising target to develop new therapeutic molecules against tuberculosis. In this study, we have screened FDA approved compounds in silico to identify inhibitors against Mtb ClpB. In our screen, several compounds interacted with ClpB. The top four compounds, namely framycetin, gentamicin, ribostamycin and tobramycin showing the highest binding energy were selected for further investigation...

In this study, we conducted Ferguson plot analyses using both agarose and polyacrylamide gels in native electrophoresis and SDS-PAGE. The results revealed intriguing differences in the behavior of bovine serum albumin (BSA) and other model proteins. Specifically, BSA exhibited Ferguson plot slopes that were dependent on the oligomer size in agarose native gel electrophoresis, while such size-dependent behavior was not observed in native-PAGE or SDS-PAGE. These findings suggest that Ferguson plot analysis is a suitable approach when using agarose gel under the electrophoretic conditions employed in this study...

OBJECTIVE: This retrospective, cross-sectional analytical study investigated the incidence of tooth agenesis in cleft lip and palate (CLP) patients. Cone Beam Computed Tomography (CBCT) radiographs of the CLP children were examined for congenitally missing teeth. METHOD: This study was conducted at three radiology centers in Lahore, namely, the Pakistan Jinnah MRI and Body Scan Centre, the University of Lahore Radiology Centres, and Fatima Memorial Hospital, from September 2021 to August 2022...

Accurate pairing of amino acids and tRNAs is a prerequisite for faithful translation of genetic information during protein biosynthesis. Here we present the effects of proteome-wide mistranslation of isoleucine (Ile) by canonical valine (Val) or non-proteinogenic norvaline (Nva) in a genetically engineered Escherichia coli strain with an editing-defective isoleucyl-tRNA synthetase (IleRS). Editing-defective IleRS efficiently mischarges both Val and Nva to tRNAIle and impairs the translational accuracy of Ile decoding...

Heat shock proteins (HSPs) are developmentally conserved families of protein found in both prokaryotic and eukaryotic organisms. HSPs are engaged in a diverse range of physiological processes, including molecular chaperone activity to assist the initial protein folding or promote the unfolding and refolding of misfolded intermediates to acquire the normal or native conformation and its translocation and prevent protein aggregation as well as in immunity, apoptosis, and autophagy. These molecular chaperonins are classified into various families according to their molecular size or weight, encompassing small HSPs (e...

Here, we studied the effect of low-shear modeled microgravity (LSMMG) on cross stress resistance (heat, acid, and oxidative), fatty acid content, and pathogenicity along with alteration in expression of stress-/virulence-associated genes in Legionella pneumophila. The stress resistance analysis result indicated that bacteria cultivated under LSMMG environments showed higher resistance with elevated D-values at 55 °C and in 1 mM of hydrogen peroxide (H2 O2 ) conditions compared to normal gravity (NG)-grown bacteria...

CLPB is a mitochondrial intermembrane space AAA+ domain-containing disaggregase. CLPB mutations are associated with 3-methylglutaconic aciduria and neutropenia; however, the molecular mechanism underscoring disease and the contribution of CLPB substrates to disease pathology remains unknown. Interactions between CLPB and mitochondrial quality control (QC) factors, including PARL and OPA1, have been reported, hinting at dysregulation of organelle QC in disease. Utilizing proteomic and biochemical approaches, we show a stress-specific aggregation phenotype in a CLPB-null environment and define the CLPB substrate profile...

The signature of selection is a crucial concept in evolutionary biology that refers to the pattern of genetic variation which arises in a population due to natural selection. In the context of climate adaptation, the signature of selection can reveal the genetic basis of adaptive traits that enable organisms to survive and thrive in changing environmental conditions. Breeds living in diverse agroecological zones exhibit genetic "footprints" within their genomes that mirror the influence of climate-induced selective pressures, subsequently impacting phenotypic variance...

OBJECTIVE: The purpose of this study was to test the effect of adding diaphragmatic breathing exercises (DBEs) to core stabilization exercises (CSEs) for patients with chronic low back pain (CLPB). METHODS: Twenty-two patients with CLPB were randomly allocated to the experimental (DBE + CSE) or control group (CSE only). They were given 12 treatment sessions 3 times a week for 4 weeks. Patients were evaluated before and after the 12 sessions. Surface electromyography of transverse abdominis, Oswestry Disability Index, Fear Avoidance Belief Questionnaire, Pittsburgh Sleep Quality Index, Numeric Pain Rating Scale, and chest expansion were used as outcome measures for pain, muscle activity, disability, and sleep quality...

AAA+ proteins (ATPases associated with various cellular activities) comprise a family of powerful ring-shaped ATP-dependent translocases that carry out numerous vital substrate-remodeling functions. ClpB is a AAA+ protein disaggregation machine that forms a two-tiered hexameric ring, with flexible pore loops protruding into its center and binding to substrate-proteins. It remains unknown whether these pore loops contribute only passively to substrate-protein threading or have a more active role. Recently, we have applied single-molecule FRET (smFRET) spectroscopy to directly measure the dynamics of substrate-binding pore loops in ClpB...

Atomic force microscopy (AFM) and high-speed AFM allow direct observation of biomolecular structures and their functional dynamics. Based on scanning the molecular surface of a sample deposited on a supporting substrate by a probing tip, topographic images of its dynamic shape are obtained. Critical to successful AFM observations is a balance between immobilization of the sample while avoiding too strong perturbations of its functional conformational dynamics. Since the sample placement on the supporting substrate cannot be directly controlled in experiments, the relative orientation is a priori unknown, and, due to limitations in the spatial resolution of images, difficult to infer from a posteriori analysis, thus hampering the interpretation of measurements...

The origin of eukaryotic cells, and especially naturally occurring syncytial cells, remains debatable. While a majority of our biomedical research focuses on the eukaryotic result of evolution, our data remain limiting on the prokaryotic precursors of these cells. This is particularly evident when considering extremophile biology, especially in how the genomes of organisms in extreme environments must have evolved and adapted to unique habitats. Might these rapidly diversifying organisms have created new genetic tools eventually used to enhance the evolution of the eukaryotic single nuclear or syncytial cells? Many organisms are capable of surviving, or even thriving, in conditions of extreme temperature, acidity, organic composition, and then rapidly adapt to yet new conditions...

BACKGROUND: The incidence of skin cutaneous melanoma (SKCM), one of the most aggressive and lethal skin tumors, is increasing worldwide. However, for advanced SKCM, we still lack an accurate and valid way to predict its prognosis, as well as novel theories to guide the planning of treatment options for SKCM patients. Lactylation (LAC), a novel post-translational modification of histones, has been shown to promote tumor growth and inhibit the antitumor response of the tumor microenvironment (TME) in a variety of ways...

Inclusion body-associated proteins IbpA and IbpB of MW 16 KDa are the two small heat-shock proteins (sHSPs) of Escherichia coli, and they have only holding, but not folding, chaperone activity. In vitro holdase activity of IbpB is more than that of IbpA, and in combination, they synergise. Both IbpA and IbpB monomers first form homodimers, which as building blocks subsequently oligomerize to make heavy oligomers with MW of MDa range; for IbpB, the MW range of heavy oligomers is 2.0-3.0 MDa, whereas for IbpA oligomers, the values in MDa are not so specified/reported...

OBJECTIVE: To explore the clinical features and genetic basis for a child with 3-methylglutaconic aciduria type VII. METHODS: A child who was diagnosed at the Gansu Provincial Maternity and Child Health Care Hospital on August 9, 2019 was selected as the study subject. Clinical data of the child, including urine gas chromatography and mass spectrometry, were collected. The child and her parents were subjected to whole exome sequencing. RESULTS: The child, a female neonate, had presented mainly with intermittent skin cyanosis, convulsions, hypomagnesemia, apnea, neutropenia after birth...

Caseinolytic peptidase B homolog (CLPB) is a mitochondrial protein which is highly expressed in brain. Its deficiency may be associated with severe neonatal encephalopathy. This report describes a case of fatal neonatal encephalopathy associated with biallelic stop-gain mutation in CLPB (NM_001258392.3:c.1159C>T/p.Arg387*). Neurologic disorder encompasses pre- and post-natal features including polyhydramnios, intrauterine growth restriction, respiratory insufficiency, lethargy, excessive startle reflex, generalized hypertonia, and epileptic seizures...

Mycoplasma contamination in cell culture affects the properties of cell lines. Gold standard detection by microbiological culture takes days and requires specialists. The polymerase chain reaction and loop-mediated isothermal amplification (LAMP) are fast molecular options, but LAMP only requires one heating block for DNA amplification. This study presents a comparative genomic analysis of Mycoplasma species to identify common target genes different from the rrsA gene, which encodes 16 S rRNA. The aim is to implement a LAMP assay to detect Mycoplasma species, reducing the time and specialized equipment required for detection...