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Current Opinion in Neurobiology Aug 2020Central nervous system function requires the proper formation and function of synapses. The α2δ auxiliary subunits of voltage-gated calcium channels have emerged as... (Review)
Review
Central nervous system function requires the proper formation and function of synapses. The α2δ auxiliary subunits of voltage-gated calcium channels have emerged as regulators of a number of critical events associated with regulation of synaptic function, including channel trafficking and localization, as well as the initial establishment of synaptic structures. In this review, we will discuss some of these recent studies which have uncovered novel mechanisms for α2δ function at the synapse, including the regulation of calcium channel α1 subunit specificity and the promotion of dendritic spine growth. Moreover, we will cover recent advances that have been made in understanding the consequences of aberrant α2δ signaling in injury and disease.
Topics: Calcium; Calcium Channels; Protein Subunits; Protein Transport; Synapses
PubMed: 32521436
DOI: 10.1016/j.conb.2020.04.007 -
Biomolecules Mar 2021The COP9 signalosome (CSN) is a highly conserved eukaryotic multi-subunit enzyme, regulating cullin RING ligase activities and accordingly, substrate ubiquitination and...
The COP9 signalosome (CSN) is a highly conserved eukaryotic multi-subunit enzyme, regulating cullin RING ligase activities and accordingly, substrate ubiquitination and degradation. We showed that the CSN complex of that is deviated in subunit composition and in sequence homology harbors a highly conserved cullin deneddylase enzymatic core complex. We took advantage of the non-essentiality of the CSN-NEDD8/Rub1 axis, together with the enzyme-substrate cross-species activity, to develop a sensitive fluorescence readout assay, suitable for biochemical assessment of cullin deneddylation by CSNs from various origins. We also demonstrated that the yeast catalytic subunit, CSN5/Jab1, is targeted by an inhibitor that was selected for the human orthologue. Treatment of yeast by the inhibitor led to the accumulation of neddylated cullins and the formation of reactive oxygen species. Overall, our data revealed as a general platform that can be used for studies of CSN deneddylation and for testing the efficacy of selected CSN inhibitors.
Topics: COP9 Signalosome Complex; Cullin Proteins; Humans; Protein Subunits; Reactive Oxygen Species; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Substrate Specificity; Ubiquitination; Ubiquitins
PubMed: 33806190
DOI: 10.3390/biom11040497 -
Proteomics Aug 2015Although the number of protein-encoding genes in the human genome is only about 20 000 not far from the amount found in the nematode worm genome, the number of proteins... (Review)
Review
Although the number of protein-encoding genes in the human genome is only about 20 000 not far from the amount found in the nematode worm genome, the number of proteins that are translated from these sequences is larger by several orders of magnitude. A number of mechanisms have evolved to enable this diversity. For example, genes can be alternatively spliced to create multiple transcripts; they may also be translated from different alternative initiation sites. After translation, hundreds of chemical modifications can be introduced in proteins, altering their chemical properties, folding, stability, and activity. The complexity is then further enhanced by the various combinations that are generated from the assembly of different subunit variants into protein complexes. This, in turn, confers structural and functional flexibility, and endows the cell with the ability to adapt to various environmental conditions. Therefore, exposing the variability of protein complexes is an important step toward understanding their biological functions. Revealing this enormous diversity, however, is not a simple task. In this review, we will focus on the array of MS-based strategies that are capable of performing this mission. We will also discuss the challenges that lie ahead, and the future directions toward which the field might be heading.
Topics: Computational Biology; Mass Spectrometry; Models, Molecular; Protein Conformation; Protein Processing, Post-Translational; Protein Subunits
PubMed: 25727951
DOI: 10.1002/pmic.201400517 -
RPS7 promotes cell migration through targeting epithelial-mesenchymal transition in prostate cancer.Urologic Oncology May 2019Small ribosomal protein subunit 7 (RPS7) is an important structural components of the ribosome involved in protein synthesis, previous studies demonstrated that RPS7 was...
OBJECTIVES
Small ribosomal protein subunit 7 (RPS7) is an important structural components of the ribosome involved in protein synthesis, previous studies demonstrated that RPS7 was associated with several malignancies, but the role of RPS7 in prostate cancer (PCa) remains unclear. To decipher such a puzzle, in the current study, we deciphered the role and mechanism of RPS7 during the progression of PCa.
MATERIAL AND METHODS
In this study, the expression of mRNA was performed by quantitative real-time PCR. The protein level was identified by Western blotting. Kaplan-Meier survival analysis was demonstrated the relation between the abnormal expression of RPS7 mRNA and the overall survival. Cell proliferation was assessed by MTT assay and cell counting, meanwhile, cell migration was checked by transwell assay.
RESULTS
RPS7 is higher expressed in PCa (p < 0.001), and the overexpression of RPS7 is closely associated with poor outcome of PCa patients after radical prostatectomy (p < 0.001). Inhibition the expression of RPS7 with a specific RPS7 siRNA could markedly attenuate prostate tumor growth and migration (p < 0.05). Mechanistic data reveals that inhibition of RPS7 could up-regulate the epithelial protein marker, E-cadherin (p < 0.05), and down-regulate the mesenchymal protein markers, such as N-cadherin and Snail (p < 0.001).
CONCLUSIONS
RPS7 is a newly verified tumor promoter in PCa, and promotes cell migration by targeting epithelial-to-mesenchymal transitionpathway. Thus, inhibition of RPS7-epithelial to-mesenchymal transition signaling might represent a prospective approach toward limiting prostate tumor progression.
Topics: Cell Movement; Cells, Cultured; Epithelial-Mesenchymal Transition; Humans; Male; Prostatic Neoplasms; Protein Subunits; Ribosomal Proteins
PubMed: 30737160
DOI: 10.1016/j.urolonc.2019.01.011 -
Viruses Dec 2022The Ebola virus has caused outbreaks in Central and West Africa, with high rates of morbidity and mortality. Clinical trials of recombinant virally vectored vaccines did...
The Ebola virus has caused outbreaks in Central and West Africa, with high rates of morbidity and mortality. Clinical trials of recombinant virally vectored vaccines did not explicitly include pregnant or nursing women, resulting in a gap in knowledge of vaccine-elicited maternal antibody and its potential transfer. The role of maternal antibody in Ebola virus disease and vaccination remains understudied. Here, we demonstrate that a protein subunit vaccine can elicit robust humoral responses in pregnant mice, which are transferred to pups in breastmilk. These findings indicate that an intramuscular protein subunit vaccine may elicit Ebola-specific IgG capable of being transferred across the placenta as well as into the breastmilk. We have previously shown protective efficacy with these vaccines in non-human primates, offering a potential safe and practical alternative to recombinant virally vectored vaccines for pregnant and nursing women in Ebola endemic regions.
Topics: Female; Animals; Mice; Ebolavirus; Hemorrhagic Fever, Ebola; Protein Subunits; Democratic Republic of the Congo; Disease Models, Animal; Ebola Vaccines; Antibodies, Viral; Immunization; Vaccination; Primates; Vaccines, Synthetic
PubMed: 36560788
DOI: 10.3390/v14122784 -
Biophysical Journal Sep 2015We present an overview of the full repertoire of intertwined associations in homooligomeric proteins. This overview summarizes recent findings on the different... (Review)
Review
We present an overview of the full repertoire of intertwined associations in homooligomeric proteins. This overview summarizes recent findings on the different categories of intertwined associations in known protein structures, their assembly modes, the properties of their interfaces, and their structural plasticity. Furthermore, the current body of knowledge on the so-called three-dimensional domain-swapped systems is reexamined in the context of the wider landscape of intertwined homooligomers, with a particular focus on the mechanistic aspects that underpin intertwined self-association processes in proteins. Insights gained from this integrated overview into the physical and biological roles of intertwining are highlighted.
Topics: Protein Multimerization; Protein Stability; Protein Subunits
PubMed: 26340815
DOI: 10.1016/j.bpj.2015.08.010 -
Philosophical Transactions of the Royal... Jun 2018Advances in native mass spectrometry and single-molecule techniques have made it possible in recent years to determine the values of successive ligand binding constants... (Review)
Review
Advances in native mass spectrometry and single-molecule techniques have made it possible in recent years to determine the values of successive ligand binding constants for large multi-subunit proteins. Given these values, it is possible to distinguish between different allosteric mechanisms and, thus, obtain insights into how various bio-molecular machines work. Here, we describe for ring-shaped homo-oligomers, in particular, how the relationship between the values of successive ligand binding constants is diagnostic for concerted, sequential and probabilistic allosteric mechanisms.This article is part of a discussion meeting issue 'Allostery and molecular machines'.
Topics: Allosteric Regulation; Humans; Ligands; Models, Molecular; Protein Binding; Protein Subunits
PubMed: 29735730
DOI: 10.1098/rstb.2017.0176 -
Zhonghua Gan Zang Bing Za Zhi =... Sep 2022To analyze guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1) expression based on bioinformatics, so as to evaluate its role and its relationship with...
To analyze guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1) expression based on bioinformatics, so as to evaluate its role and its relationship with survival rate during the occurrence and development of hepatocellular carcinoma. GEPIA, UALCAN and HPA databases were used to analyze the expression level of GNB2L1 and its relationship with HCC survival rate. Mutations in the GNB2L1 gene and their impact on survival were analyzed using the cBioPortal database. LinkedOmics database was used to analyze GNB2L1-related genes in HCC. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed simultaneously. STEING database was used to construct the GNB2L1 protein interaction network. TIMER database was used to analyze the relationship between GNB2L1 gene expression and immune infiltration in hepatocellular carcinoma. Differential expression of GNB2L1 in plasma platelets of HCC patients and healthy controls was analyzed using mRNA-based sequencing technology. Data between groups were compared using an independent-samples -test. GNB2L1 expression level was significantly increased in HCC tissues (<0.05), and its expression was significantly correlated with body weight, classification and stage (<0.05). The overall survival rate was higher in GNB2L1 low expression group (<0.001). GNB2L1 and its related genes were related to biological process regulation, metabolic process, protein binding, oxidative phosphorylation, JAK-STAT signaling pathway, Ras signaling pathway and so on. GNB2L1 had interaction with RPS12, RPS11 and RPL19, and participated in multiple biological processes such as liver regeneration and positive regulation of endogenous apoptotic signaling pathway. GNB2L1 expression was significantly positively correlated with the infiltration degree of various immune cells in HCC (<0.05). Cox regression analysis showed that GNB2L1 was an independent risk factor for lower survival rate in patients with HCC [Hazard ratio (95% confidence interval)=1.456 (1.034~2.051), =0.031]. GNB2L1expression levels were significantly higher in platelets of HCC patients than that of healthy controls (10.40±1.36 . 9.58±0.51, =2.194, =0.037). GNB2L1 has high expression and close relationship to survival rate in HCC. Therefore, GNB2L1 may be a potential biomarker of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Computational Biology; Liver Neoplasms; Protein Subunits; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; RNA, Messenger; Guanine Nucleotides; Gene Expression; Biomarkers, Tumor
PubMed: 36299189
DOI: 10.3760/cma.j.cn501113-20211014-00509 -
Emerging Microbes & Infections Dec 2022Analysis of large-scale gene expression post vaccination can provide an overview of immune responses. We used transcriptional approaches to comprehensively analyze the...
Analysis of large-scale gene expression post vaccination can provide an overview of immune responses. We used transcriptional approaches to comprehensively analyze the innate immune response signatures elicited by protein subunit (PS) vaccine ZF2001 and an mRNA vaccine named RRV. A fine-grained time-dependent dissection of large-scale gene expression post immunization revealed that ZF001 induced MHC class II-related genes, including and , more expeditiously than the RRV. Notably, the RRV induced MHC class I-related genes such as /, and /. At day 21 post immunization, the titres of binding and neutralization antibody (NAb) induced by both vaccines were comparable, which were accordant with the expression level of genes essential to BCR/TCR signalling transduction and B/T cells activation at day 7. However, compared to ZF2001, the early responses of RRV were more robust, including the activation of pattern recognition receptors (PRRs), expression of genes involved in RNA degradation, and transcription inhibition, which are directly related to anti-viral signals. This pattern also coincided with the induction of cytokines by the RRV. Generally, the transcriptomic patterns of two very different vaccines mapped here provide a framework for establishing correlates between the induction of genes and protection, which can be tailored for evoking specific and potent immune responses against SARS-CoV-2.
Topics: Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Humans; Immunity, Innate; Protein Subunits; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Transcriptome; Vaccination; Vaccines, Subunit; Vaccines, Synthetic; mRNA Vaccines
PubMed: 35343384
DOI: 10.1080/22221751.2022.2059404 -
Open Biology Mar 2016Mitosis is a highly regulated process that allows the equal distribution of the genetic material to the daughter cells. Chromosome segregation requires the formation of...
Mitosis is a highly regulated process that allows the equal distribution of the genetic material to the daughter cells. Chromosome segregation requires the formation of a bipolar mitotic spindle and assembly of a multi-protein structure termed the kinetochore to mediate attachments between condensed chromosomes and spindle microtubules. In budding yeast, a single microtubule attaches to each kinetochore, necessitating robustness and processivity of this kinetochore-microtubule attachment. The yeast kinetochore-localized Dam1 complex forms a direct interaction with the spindle microtubule. In vitro, the Dam1 complex assembles as a ring around microtubules and couples microtubule depolymerization with cargo movement. However, the subunit organization within the Dam1 complex, its higher-order oligomerization and how it interacts with microtubules remain under debate. Here, we used chemical cross-linking and mass spectrometry to define the architecture and subunit organization of the Dam1 complex. This work reveals that both the C termini of Duo1 and Dam1 subunits interact with the microtubule and are critical for microtubule binding of the Dam1 complex, placing Duo1 and Dam1 on the inside of the ring structure. Integrating this information with available structural data, we provide a coherent model for how the Dam1 complex self-assembles around microtubules.
Topics: Fungal Proteins; Kinetochores; Microtubules; Models, Molecular; Protein Binding; Protein Interaction Maps; Protein Subunits; Saccharomycetales
PubMed: 26962051
DOI: 10.1098/rsob.150237