Project description:Protein arginine methyltransferases (PRMTs) are a family of enzymes that can methylate arginine residues on histones and other proteins. PRMTs play a crucial role in influencing various cellular functions, including cellular development and tumorigenesis. Arginine methylation by PRMTs is found on both nuclear and cytoplasmic proteins. Recently, there is increasing evidence regarding post-translational modifications of non-histone proteins by PRMTs, illustrating the previously unknown importance of PRMTs in the regulation of various cellular functions by post-translational modifications. In this review, we present the recent developments in the regulation of non-histone proteins by PRMTs.
Project description:BackgroundRods and cones are photoreceptor neurons in the retina that are required for visual sensation in vertebrates, wherein the perception of vision is initiated when these neurons respond to photons in the light stimuli. The photoreceptor cell is structurally studied as outer segments (OS) and inner segments (IS) where proper protein sorting, localization, and compartmentalization are critical for phototransduction, visual function, and survival. In human retinal diseases, improper protein transport to the OS or mislocalization of proteins to the IS and other cellular compartments could lead to impaired visual responses and photoreceptor cell degeneration that ultimately cause loss of visual function.ResultsTherefore, studying and identifying mechanisms involved in facilitating and maintaining proper protein transport in photoreceptor cells would help our understanding of pathologies involving retinal cell degeneration in inherited retinal dystrophies, age-related macular degeneration, and Usher Syndrome.ConclusionsOur mini-review will discuss mechanisms of protein transport within photoreceptors and introduce a novel role for an unconventional motor protein, MYO1C, in actin-based motor transport of the visual chromophore Rhodopsin to the OS, in support of phototransduction and visual function.
Project description:The Hsp70 family of molecular chaperones acts as a central 'hub' in the cell that interacts with numerous newly synthesized proteins to assist in their biogenesis. Apart from its central and well-established role in facilitating protein folding, Hsp70s also act as key decision points in the cellular chaperone network that direct client proteins to distinct biogenesis and quality control pathways. In this paper, we review accumulating data that illustrate a new branch in the Hsp70 network: the post-translational targeting of nascent membrane and organellar proteins to diverse cellular organelles. Work in multiple pathways suggests that Hsp70, via its ability to interact with components of protein targeting and translocation machineries, can initiate elaborate substrate relays in a sophisticated cascade of chaperones, cochaperones, and receptor proteins, and thus provide a mechanism to safeguard and deliver nascent membrane proteins to the correct cellular membrane. We discuss the mechanistic principles gleaned from better-studied Hsp70-dependent targeting pathways and outline the observations and outstanding questions in less well-studied systems.
Project description:Copper is an essential trace element for human biology where its metal dyshomeostasis accounts for an increased level of serum copper, which accelerates protein aggregation. Protein aggregation is a notable feature for many neurodegenerative disorders. Herein, we report an experimental study using two model proteins, bovine serum albumin (BSA) and human serum albumin (HSA), to elucidate the mechanistic pathway by which serum albumins get converted from a fully folded globular protein to a fibril and an amorphous aggregate upon interaction with copper. Steady-state fluorescence, time-resolved fluorescence studies, and Raman spectroscopy were used to monitor the unfolding of serum albumin with increasing copper concentrations. Steady-state fluorescence studies have revealed that the fluorescence quenching of BSA/HSA by Cu(II) has occurred through a static quenching mechanism, and we have evaluated both the quenching constants individually. The binding constants of BSA-Cu(II) and HSA-Cu(II) were found to be 2.42 × 104 and 0.05 × 104 M-1, respectively. Further nanoscale morphological changes of BSA mediated by oligomers to fibril and HSA to amorphous aggregate formation were studied using atomic force microscopy. This aggregation process correlates with the Stern-Volmer plots in the absence of discernible lag phase. Raman spectroscopy results obtained are in good agreement with the increase in antiparallel β-sheet structures formed during the aggregation of BSA in the presence of Cu(II) ions. However, an increase in α-helical fractions is observed for the amorphous aggregate formed from HSA.
Project description:During activation of the spliceosome, the U4/U6 snRNA duplex is dissociated, releasing U6 for subsequent base pairing with U2 snRNA. Proteins that directly bind the U4/U6 interaction domain potentially could mediate these structural changes. We thus investigated binding of the human U4/U6-specific proteins, 15.5K, 61K and the 20/60/90K protein complex, to U4/U6 snRNA in vitro. We demonstrate that protein 15.5K is a nucleation factor for U4/U6 snRNP assembly, mediating the interaction of 61K and 20/60/90K with U4/U6 snRNA. A similar hierarchical assembly pathway is observed for the U4atac/U6atac snRNP. In addition, we show that protein 61K directly contacts the 5' portion of U4 snRNA via a novel RNA-binding domain. Furthermore, the 20/60/90K heteromer requires stem II but not stem I of the U4/U6 duplex for binding, and this interaction involves a direct contact between protein 90K and U6. This uneven clustering of the U4/U6 snRNP-specific proteins on U4/U6 snRNA is consistent with a sequential dissociation of the U4/U6 duplex prior to spliceosome catalysis.
Project description:The arrestin clan can now be broadly divided into three structurally similar subgroups: the originally identified arrestins (visual and β-arrestins), the α-arrestins and a group of Vps26-related proteins. The visual and β-arrestins selectively bind to agonist-occupied phosphorylated G protein-coupled receptors (GPCRs) and inhibit GPCR coupling to heterotrimeric G proteins while the β-arrestins also function as adaptor proteins to regulate GPCR trafficking and G protein-independent signaling. The α-arrestins have also recently been implicated in regulating GPCR trafficking while Vps26 regulates retrograde trafficking. In this review, we provide an overview of the α-arrestins and β-arrestins with a focus on our current understanding of how these adaptor proteins regulate GPCR trafficking.
Project description:Activator protein-1 (AP-1) regulates a wide range of cellular processes including proliferation, differentiation, and apoptosis. As a transcription factor, AP-1 is commonly found as a heterodimer comprised of c-Jun and c-Fos proteins. However, other heterodimers may also be formed. The function of these dimers, specifically the heterodimeric AP-1 comprised of JunD and c-Fos (AP-1(JunD/c-Fos)), has not been elucidated. Here, we identified a function of AP-1(JunD/c-Fos) in Xenopus hematopoiesis. A gain-of-function study performed by overexpressing junD and c-fos and a loss-of-function study using morpholino junD demonstrate a critical role for AP-1(JunD/c-Fos) in hematopoiesis during Xenopus embryogenesis. Additionally, we confirmed that JunD of AP-1(JunD/c-Fos) is required for BMP-4-induced hematopoiesis. We also demonstrated that BMP-4 regulated JunD activity at the transcriptional regulation and post-translational modification levels. Collectively, our findings identify AP-1(JunD/c-Fos) as a novel hematopoietic transcription factor and the requirement of AP-1(JunD/c-Fos) in BMP-4-induced hematopoiesis during Xenopus hematopoiesis.
Project description:Microarray technology has been successfully used in many biology studies to solve the protein-protein interaction (PPI) prediction computationally. For normal tissue, the cell regulation process begins with transcription and ends with the translation process. However, when cell regulation activity goes wrong, cancer occurs. Microarray data can precisely give high accuracy expression levels at normal and cancer-affected cells, which can be useful for the identification of disease-related genes. First, the differentially expressed genes (DEGs) are extracted from the cancer microarray dataset in order to identify the genes that are up-regulated and down-regulated during cancer progression in the human body. Then, proteins corresponding to these genes are collected from NCBI, and then the STRING web server is used to build the PPI network of these proteins. Interestingly, up-regulated proteins have always a higher number of PPIs compared to down-regulated proteins, although, in most of the datasets, the majority of these DEGs are down-regulated. We hope this study will help to build a relevant model to analyze the process of cancer progression in the human body.
Project description:Cadmium-bearing nanoparticles, such as nanoparticulate cadmium selenide (CdSe) and cadmium sulfide (CdS), widely exist in the environment and originate from both natural and anthropogenic sources. Risk assessment of these nanoparticles cannot be accurate without taking into account the properties of the protein corona that is acquired by the nanoparticles upon biouptake. Here, we show that the compositions of the protein corona on CdSe/CdS nanoparticles are regulated collectively by the surface atomic arrangement of the nanoparticles and the abundance and distribution of cysteine moieties of the proteins in contact with the nanoparticles. A proteomic analysis shows that the observed facet-dependent preferential binding of proteins is mostly related to the cysteine contents of the proteins, among commonly recognized protein properties controlling the formation of the protein corona. Theoretical calculations further demonstrate that the atomic arrangement of surface Cd atoms, as dictated by the exposed facets of the nanoparticles, controls the specific binding mode of the S atoms in the disulfide bonds of the proteins. Supplemental protein adsorption experiments confirm that disulfide bonds remain intact during protein adsorption, making the binding of protein molecules sensitive to the abundance and distribution of Cd-binding moieties and possibly molecular rigidity of the proteins. The significant conformational changes of adsorbed proteins evidenced from a circular dichroism spectroscopy analysis suggest that disrupting the structural stability of proteins may be an additional risk factor of Cd-bearing nanoparticles. These findings underline that the unique properties and behaviors of nanoparticles must be fully considered when evaluating the biological effects and health risks of metal pollutants.
Project description:Bacterial cell division typically requires assembly of the cytoskeletal protein FtsZ into a ring (Z-ring) at the nascent division site that serves as a foundation for assembly of the division apparatus. High resolution imaging suggests that the Z-ring consists of short, single-stranded polymers held together by lateral interactions. Several proteins implicated in stabilizing the Z-ring enhance lateral interactions between FtsZ polymers in vitro. Here we report that residues at the C terminus of Bacillus subtilis FtsZ (C-terminal variable region (CTV)) are both necessary and sufficient for stimulating lateral interactions in vitro in the absence of modulatory proteins. Swapping the 6-residue CTV from B. subtilis FtsZ with the 4-residue CTV from Escherichia coli FtsZ completely abolished lateral interactions between chimeric B. subtilis FtsZ polymers. The E. coli FtsZ chimera readily formed higher order structures normally seen only in the presence of molecular crowding agents. CTV-mediated lateral interactions are important for the integrity of the Z-ring because B. subtilis cells expressing the B. subtilis FtsZ chimera had a low frequency of FtsZ ring formation and a high degree of filamentation relative to wild-type cells. Site-directed mutagenesis of the B. subtilis CTV suggests that electrostatic forces are an important determinant of lateral interaction potential.