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FEMS Microbiology Reviews Sep 2017Pseudomonas aeruginosa is a Gram-negative bacterium belonging to the γ-proteobacteria. Like other members of the Pseudomonas genus, it is known for its metabolic... (Review)
Review
Pseudomonas aeruginosa is a Gram-negative bacterium belonging to the γ-proteobacteria. Like other members of the Pseudomonas genus, it is known for its metabolic versatility and its ability to colonize a wide range of ecological niches, such as rhizosphere, water environments and animal hosts, including humans where it can cause severe infections. Another particularity of P. aeruginosa is its high intrinsic resistance to antiseptics and antibiotics, which is partly due to its low outer membrane permeability. In contrast to Enterobacteria, pseudomonads do not possess general diffusion porins in their outer membrane, but rather express specific channel proteins for the uptake of different nutrients. The major outer membrane 'porin', OprF, has been extensively investigated, and displays structural, adhesion and signaling functions while its role in the diffusion of nutrients is still under discussion. Other porins include OprB and OprB2 for the diffusion of glucose, the two small outer membrane proteins OprG and OprH, and the two porins involved in phosphate/pyrophosphate uptake, OprP and OprO. The remaining nineteen porins belong to the so-called OprD (Occ) family, which is further split into two subfamilies termed OccD (8 members) and OccK (11 members). In the past years, a large amount of information concerning the structure, function and regulation of these porins has been published, justifying why an updated review is timely.
Topics: Bacterial Proteins; Gene Expression Regulation, Bacterial; Porins; Protein Conformation; Pseudomonas aeruginosa
PubMed: 28981745
DOI: 10.1093/femsre/fux020 -
Sub-cellular Biochemistry 2019The transport of small molecules across membranes is essential for the import of nutrients and other energy sources into the cell and, for the export of waste and other... (Review)
Review
The transport of small molecules across membranes is essential for the import of nutrients and other energy sources into the cell and, for the export of waste and other potentially harmful byproducts out of the cell. While hydrophobic molecules are permeable to membranes, ions and other small polar molecules require transport via specialized membrane transport proteins . The two major classes of membrane transport proteins are transporters and channels. With our focus here on porins-major class of non-specific diffusion channel proteins , we will highlight some recent structural biology reports and functional assays that have substantially contributed to our understanding of the mechanism that mediates uptake of small molecules, including antibiotics, across the outer membrane of Enterobacteriaceae . We will also review advances in the regulation of porin expression and porin biogenesis and discuss these pathways as new therapeutic targets.
Topics: Anti-Bacterial Agents; Biological Transport; Enterobacteriaceae; Porins
PubMed: 31214985
DOI: 10.1007/978-3-030-18768-2_4 -
Biological Chemistry May 2020Mitochondria import the vast majority of their proteins via dedicated protein machineries. The translocase of the outer membrane (TOM complex) forms the main entry site... (Review)
Review
Mitochondria import the vast majority of their proteins via dedicated protein machineries. The translocase of the outer membrane (TOM complex) forms the main entry site for precursor proteins that are produced on cytosolic ribosomes. Subsequently, different protein sorting machineries transfer the incoming preproteins to the mitochondrial outer and inner membranes, the intermembrane space, and the matrix. In this review, we highlight the recently discovered role of porin, also termed voltage-dependent anion channel (VDAC), in mitochondrial protein biogenesis. Porin forms the major channel for metabolites and ions in the outer membrane of mitochondria. Two different functions of porin in protein translocation have been reported. First, it controls the formation of the TOM complex by modulating the integration of the central receptor Tom22 into the mature translocase. Second, porin promotes the transport of carrier proteins toward the carrier translocase (TIM22 complex), which inserts these preproteins into the inner membrane. Therefore, porin acts as a coupling factor to spatially coordinate outer and inner membrane transport steps. Thus, porin links metabolite transport to protein import, which are both essential for mitochondrial function and biogenesis.
Topics: Humans; Mitochondria; Mitochondrial Proteins; Porins; Protein Transport; Saccharomyces cerevisiae
PubMed: 31967957
DOI: 10.1515/hsz-2019-0438 -
Methods in Molecular Biology (Clifton,... 2019Neisseria gonorrhoeae infection is a major public health problem worldwide. The increasing incidence of gonorrhea coupled with global spread of multidrug-resistant... (Review)
Review
Neisseria gonorrhoeae infection is a major public health problem worldwide. The increasing incidence of gonorrhea coupled with global spread of multidrug-resistant isolates of gonococci has ushered in an era of potentially untreatable infection. Gonococcal disease elicits limited immunity, and individuals are susceptible to repeated infections. In this chapter, we describe gonococcal disease and epidemiology and the structure and function of major surface components involved in pathogenesis. We also discuss the mechanisms that gonococci use to evade host immune responses and the immune responses following immunization with selected bacterial components that may overcome evasion. Understanding the biology of the gonococcus may aid in preventing the spread of gonorrhea and also facilitate the development of gonococcal vaccines and treatments.
Topics: Bacterial Proteins; Bacterial Vaccines; Fimbriae, Bacterial; Global Burden of Disease; Gonorrhea; Humans; Immune Evasion; Incidence; Lipopolysaccharides; Neisseria gonorrhoeae; Porins
PubMed: 31119614
DOI: 10.1007/978-1-4939-9496-0_1 -
Biochemical Society Transactions Dec 2021Pore-forming proteins (PFPs) are a broad class of molecules that comprise various families, structural folds, and assembly pathways. In nature, PFPs are most often... (Review)
Review
Pore-forming proteins (PFPs) are a broad class of molecules that comprise various families, structural folds, and assembly pathways. In nature, PFPs are most often deployed by their host organisms to defend against other organisms. In humans, this is apparent in the immune system, where several immune effectors possess pore-forming activity. Furthermore, applications of PFPs are found in next-generation low-cost DNA sequencing, agricultural crop protection, pest control, and biosensing. The advent of cryoEM has propelled the field forward. Nevertheless, significant challenges and knowledge-gaps remain. Overcoming these challenges is particularly important for the development of custom, purpose-engineered PFPs with novel or desired properties. Emerging single-molecule techniques and methods are helping to address these unanswered questions. Here we review the current challenges, problems, and approaches to studying PFPs.
Topics: Cryoelectron Microscopy; DNA; High-Throughput Nucleotide Sequencing; Humans; Porins
PubMed: 34747994
DOI: 10.1042/BST20210706 -
Nano Letters Oct 2023Nucleoside drugs, which are analogues of natural nucleosides, have been widely applied in the clinical treatment of viral infections and cancers. The development of...
Nucleoside drugs, which are analogues of natural nucleosides, have been widely applied in the clinical treatment of viral infections and cancers. The development of nucleoside drugs, repurposing of existing drugs, and combined use of multiple drug types have made the rapid sensing of nucleoside drugs urgently needed. Nanopores are emerging single-molecule sensors that have high resolution to resolve even minor structural differences between chemical compounds. Here, an engineered porin A hetero-octamer was used to perform general nucleoside drug analysis. Ten nucleoside drugs were simultaneously detected and fully discriminated. An accuracy of >99.9% was consequently reported. This sensing capacity was further demonstrated in direct nanopore analysis of ribavirin buccal tablets, confirming its sensing reliability against complex samples and environments. No sample separation is needed, however, significantly minimizing the complexity of the measurement. This technique may inspire nanopore applications in pharmaceutical production and pharmacokinetics measurements.
Topics: Nanopores; Nucleosides; Reproducibility of Results; Porins; Mycobacterium smegmatis
PubMed: 37818841
DOI: 10.1021/acs.nanolett.3c02872 -
Nature Microbiology Aug 2021Fusobacterium nucleatum, long known as a constituent of the oral microflora, has recently garnered renewed attention for its association with several different human...
Fusobacterium nucleatum, long known as a constituent of the oral microflora, has recently garnered renewed attention for its association with several different human cancers. The growing interest in this emerging cancer-associated bacterium contrasts with a paucity of knowledge about its basic gene expression features and physiological responses. As fusobacteria lack all established small RNA-associated proteins, post-transcriptional networks in these bacteria are also unknown. In the present study, using differential RNA-sequencing, we generate high-resolution global RNA maps for five clinically relevant fusobacterial strains-F. nucleatum subspecies nucleatum, animalis, polymorphum and vincentii, as well as F. periodonticum-for early, mid-exponential growth and early stationary phase. These data are made available in an online browser, and we use these to uncover fundamental aspects of fusobacterial gene expression architecture and a suite of non-coding RNAs. Developing a vector for functional analysis of fusobacterial genes, we discover a conserved fusobacterial oxygen-induced small RNA, FoxI, which serves as a post-transcriptional repressor of the major outer membrane porin FomA. Our findings provide a crucial step towards delineating the regulatory networks enabling F. nucleatum adaptation to different environments, which may elucidate how these bacteria colonize different compartments of the human body.
Topics: Bacterial Proteins; Fusobacterium Infections; Fusobacterium nucleatum; Humans; Neoplasms; Porins; RNA, Bacterial
PubMed: 34239075
DOI: 10.1038/s41564-021-00927-7 -
Oncogene Dec 2014Mitochondria, the key bioenergetic intracellular organelles, harbor a number of proteins with proven or hypothetical ion channel functions. Growing evidence points to... (Review)
Review
Mitochondria, the key bioenergetic intracellular organelles, harbor a number of proteins with proven or hypothetical ion channel functions. Growing evidence points to the important contribution of these channels to the regulation of mitochondrial function, such as ion homeostasis imbalances profoundly affecting energy transducing processes, reactive oxygen species production and mitochondrial integrity. Given the central role of mitochondria in apoptosis, their ion channels with the potential to compromise mitochondrial function have become promising targets for the treatment of malignancies. Importantly, in vivo evidence demonstrates the involvement of the proton-transporting uncoupling protein, a mitochondrial potassium channel, the outer membrane located porin and the permeability transition pore in tumor progression/control. In this review, we focus on mitochondrial channels that have been assigned a definite role in cell death regulation and possess clear oncological relevance. Overall, based on in vivo and in vitro genetic and pharmacological evidence, mitochondrial ion channels are emerging as promising targets for cancer treatment.
Topics: Animals; Apoptosis; Calcium; Cell Death; Homeostasis; Humans; Ion Channels; Mice; Mitochondria; Mitochondrial Proteins; Neoplasms; Permeability; Porins; Potassium Channels; Reactive Oxygen Species; Uncoupling Protein 1
PubMed: 24469031
DOI: 10.1038/onc.2013.578 -
Biochemical Society Transactions Oct 2019Mitochondria are essential eukaryotic organelles responsible for primary cellular energy production. Biogenesis, maintenance, and functions of mitochondria require... (Review)
Review
Mitochondria are essential eukaryotic organelles responsible for primary cellular energy production. Biogenesis, maintenance, and functions of mitochondria require correct assembly of resident proteins and lipids, which require their transport into and within mitochondria. Mitochondrial normal functions also require an exchange of small metabolites between the cytosol and mitochondria, which is primarily mediated by a metabolite channel of the outer membrane (OM) called porin or voltage-dependent anion channel. Here, we describe recently revealed novel roles of porin in the mitochondrial protein and lipid transport. First, porin regulates the formation of the mitochondrial protein import gate in the OM, the translocase of the outer membrane (TOM) complex, and its dynamic exchange between the major form of a trimer and the minor form of a dimer. The TOM complex dimer lacks a core subunit Tom22 and mediates the import of a subset of mitochondrial proteins while the TOM complex trimer facilitates the import of most other mitochondrial proteins. Second, porin interacts with both a translocating inner membrane (IM) protein like a carrier protein accumulated at the small TIM chaperones in the intermembrane space and the TIM22 complex, a downstream translocator in the IM for the carrier protein import. Porin thereby facilitates the efficient transfer of carrier proteins to the IM during their import. Third, porin facilitates the transfer of lipids between the OM and IM and promotes a back-up pathway for the cardiolipin synthesis in mitochondria. Thus, porin has roles more than the metabolite transport in the protein and lipid transport into and within mitochondria, which is likely conserved from yeast to human.
Topics: Biological Transport; Cell Cycle; Lipid Metabolism; Mitochondria; Mitochondrial Proteins; Porins
PubMed: 31670371
DOI: 10.1042/BST20190153 -
Journal of Bioenergetics and... Dec 2022Salinibacter ruber is an extremophilic bacterium able to grow in high-salts environments, such as saltern crystallizer ponds. This halophilic bacterium is red-pigmented...
Salinibacter ruber is an extremophilic bacterium able to grow in high-salts environments, such as saltern crystallizer ponds. This halophilic bacterium is red-pigmented due to the production of several carotenoids and their derivatives. Two of these pigment molecules, salinixanthin and retinal, are reported to be essential cofactors of the xanthorhodopsin, a light-driven proton pump unique to this bacterium. Here, we isolate and characterize an outer membrane porin-like protein that retains salinixanthin. The characterization by mass spectrometry identified an unknown protein whose structure, predicted by AlphaFold, consists of a 8 strands beta-barrel transmembrane organization typical of porins. The protein is found to be part of a functional network clearly involved in the outer membrane trafficking. Cryo-EM micrographs showed the shape and dimensions of a particle comparable with the ones of the predicted structure. Functional implications, with respect to the high representativity of this protein in the outer membrane fraction, are discussed considering its possible role in primary functions such as the nutrients uptake and the homeostatic balance. Finally, also a possible involvement in balancing the charge perturbation associated with the xanthorhodopsin and ATP synthase activities is considered.
Topics: Porins; Bacteroidetes; Carotenoids
PubMed: 36229623
DOI: 10.1007/s10863-022-09950-7