Beta barrell membrane protein

U-Omp19 is a bacterial protease inhibitor from Brucella abortus that inhibits gastrointestinal and lysosomal proteases, enhancing the half-life and immunogenicity of co-delivered antigens. U-Omp19 is a novel adjuvant that is in preclinical development with various vaccine candidates. However, the molecular mechanisms by which it exerts these functions and the structural elements responsible for these activities remain unknown. In this work, a structural, biochemical, and functional characterization of U-Omp19 is presented...

Fatty acids (FA) play an important role in biological functions, such as membrane homeostasis, metabolism, and as signaling molecules. FadL is the only known protein that uptakes long-chain fatty acids in Gram-negative bacteria, and this uptake has traditionally been thought to be limited to fatty acids up to 18 carbon atoms in length. Recently however, it was found Vibrio cholerae has the ability to uptake fatty acids greater than 18 carbon atoms and this uptake corresponds to bacterial survivability. Using E...

To exchange and communicate with their surroundings, bacteria have evolved multiple active and passive mechanisms for trans-envelope transport. Among the pore-forming complexes found in the outer membrane of Gram-negative bacteria, secretins are distinctive homo-oligomeric channels dedicated to the active translocation of voluminous structures such as folded proteins, assembled fibers, virus particles or DNA. Members of the bacterial secretin family share a common cylinder-shaped structure with a gated pore-forming part inserted in the outer membrane, and a periplasmic channel connected to the inner membrane components of the corresponding nanomachine...

In Gram-negative bacteria, secreted polysaccharides have multiple critical functions. In Wzx/Wzy- and ABC transporter-dependent pathways, an outer membrane (OM) polysaccharide export (OPX) type translocon exports the polysaccharide across the OM. The paradigm OPX protein Wza of Escherichia coli is an octamer in which the eight C-terminal domains form an α-helical OM pore and the eight copies of the three N-terminal domains (D1 to D3) form a periplasmic cavity. In synthase-dependent pathways, the OM translocon is a 16- to 18-stranded β-barrel protein...

BACKGROUND: Despite the immense importance of transmembrane proteins (TMP) for molecular biology and medicine, experimental 3D structures for TMPs remain about 4-5 times underrepresented compared to non-TMPs. Today's top methods such as AlphaFold2 accurately predict 3D structures for many TMPs, but annotating transmembrane regions remains a limiting step for proteome-wide predictions. RESULTS: Here, we present TMbed, a novel method inputting embeddings from protein Language Models (pLMs, here ProtT5), to predict for each residue one of four classes: transmembrane helix (TMH), transmembrane strand (TMB), signal peptide, or other...

The outer membrane of Gram-negative bacteria acts as an additional diffusion barrier for solutes and nutrients. It is perforated by outer membrane proteins (OMPs) that function most often as diffusion pores, but sometimes also as parts of larger cellular transport complexes, structural components of the cell wall, or even as enzymes. These OMPs often have large loops that protrude into the extracellular environment, which have promise for biotechnological applications and as therapeutic targets. Thus, understanding how modifications to these loops affect OMP stability and folding is critical for their efficient application...

The outer membrane proteins (OMPs) of Treponema pallidum subsp. Pallidum (T. pallidum), the etiological agent of the sexually transmitted disease syphilis, has long been a hot research topic. Despite many hurdles to studying the pathogen, especially the inability to manipulate T. pallidum in vitro genetically1, considerable progress has been made in elucidating the structure, pathogenesis, and functions of T. pallidum OMPs. In this review, we integrate this information to garner fresh insights into the role of OMPs in the diagnosis, pathogenicity, and vaccine development of T...

The recombinant OmpF porin of Yersinia pseudotuberculosis as a model of transmembrane protein of the β-barrel structural family was used to study low growth temperature effect on the structure of the produced inclusion bodies (IBs). This porin showed a very low expression level in E. coli at a growth temperature below optimal 37 °C. The introduction of a N-terminal hexahistidine tag into the mature porin molecule significantly increased the biosynthesis of the protein at low cultivation temperatures. The recombinant His-tagged porin (rOmpF-His) was expressed in E...

The simplest class of mitochondrion-related organelles (MROs) is the mitosome, an organelle present in a few anaerobic protozoan parasites such as Entamoeba histolytica, Giardia intestinalis, and Cryptosporidium parvum. E. histolytica causes amoebiasis in humans, deemed as one of the important, yet neglected tropical infections in the world. Much of the enigma of the E. histolytica mitosome circles around the obvious lack of a majority of known mitochondrial components and functions exhibited in other organisms...

Protein folding in the cell is largely a co-translational process occurring during protein synthesis on the ribosome. It has become evident that co-translational folding is characteristic to almost every protein in the cell of pro- and eukaryotic origin that are single and multidomain, single and multisubunit, cytosolic, secretory and membrane. Co-translational protein folding begins very early during the process of polypeptide chain synthesis on the ribosome, with some secondary structure elements forming inside the ribosomal tunnel and some tertiary structures forming inside the vestibule (lower/wider) region of the ribosomal exit tunnel...

BACKGROUND: The amyloid channel theory readily explains primary molecular damage induced by beta-amyloid (Aβ) but cannot interpret multiple major phenomena associated with Alzheimer's Disease such as autophagy failure and decreased metabolism. To explain them, the amyloid degradation toxicity hypothesis suggests that the cytotoxicity is initiated by the channel formation in lysosomal membranes by amyloid fragments (such as Aβ25-35 ) produced by the digestion of endocytosed Aβ. One amyloid channel is sufficient to neutralize lysosomal content and inactivate proteases; therefore, undigested amyloid accumulates, and autophagy stalls...

Pore-forming proteins (PFPs) of the diverse life forms have emerged as the potent cell-killing entities owing to their specialized membrane-damaging properties. PFPs have the unique ability to perforate the plasma membranes of their target cells, and they exert this functionality by creating oligomeric pores in the membrane lipid bilayer. Pathogenic bacteria employ PFPs as toxins to execute their virulence mechanisms, whereas in the higher vertebrates PFPs are deployed as the part of the immune system and to generate inflammatory responses...

Leptospirosis is an emerging infectious disease caused by pathogenic Leptospira spp. A universal vaccine against leptospirosis is likely to require highly conserved epitopes from pathogenic leptospires that are exposed on the bacterial surface and that generate a protective and sterilizing immune response. Our group recently identified several genes predicted to encode TonB-dependent receptors (TBDR) in Leptospira interrogans using a reverse vaccinology approach. Three leptospiral TBDRs were previously described and partially characterized as ferric-citrate, hemin, and cobalamin transporters...

Hidden Markov Models (HMMs) are amongst the most successful methods for predicting protein features in biological sequence analysis. However, there are biological problems where the Markovian assumption is not sufficient since the sequence context can provide useful information for prediction purposes. Several extensions of HMMs have appeared in the literature in order to overcome their limitations. We apply here a hybrid method that combines HMMs and Neural Networks (NNs), termed Hidden Neural Networks (HNNs), for biological sequence analysis in a straightforward manner...

Alzheimer's disease (AD) is the most common cause of dementia affecting millions of people. Neuronal death in AD is initiated by oligomeric amyloid-β (Aβ) peptides. Recently, we proposed the amyloid degradation toxicity hypothesis, which explains multiple major observations associated with AD including autophagy failure and a decreased metabolism. According to the hypothesis, the key event in the cellular toxicity of amyloid is the formation of non-selective membrane channels in lysosomal membranes by amyloid fragments that are produced by the digestion of Aβ previously absorbed by endocytosis...

NMR studies can provide unique information about protein conformations in solution. In CASP14, three reference structures provided by solution NMR methods were available (T1027, T1029, and T1055), as well as a fourth data set of NMR-derived contacts for an integral membrane protein (T1088). For the three targets with NMR-based structures, the best prediction results ranged from very good (GDT_TS = 0.90, for T1055) to poor (GDT_TS = 0.47, for T1029). We explored the basis of these results by comparing all CASP14 prediction models against experimental NMR data...

Voltage dependent anion-selective channel (VDAC) is the most abundant protein in the mitochondrial outer membrane. It is a membrane embedded β-barrel protein composed of 19 mostly anti-parallel β-strands that form a hydrophilic pore. Similar to the vast majority of mitochondrial proteins, VDAC is encoded by nuclear DNA, and synthesized on cytosolic ribosomes. The protein is then targeted to the mitochondria while being maintained in an import competent conformation by specific cytosolic factors. Recent studies, using yeast cells as a model system, have unearthed the long searched for mitochondrial targeting signal for VDAC and the role of cytosolic chaperones and mitochondrial import machineries in its proper biogenesis...

β-barrel membrane proteins have several important biological functions, including transporting water and solutes across the membrane. They are active in the highly hydrophobic environment of the lipid membrane, as opposed to soluble proteins, which function in a more polar, aqueous environment. Globular soluble proteins typically have a hydrophobic core and a polar surface that interacts favorably with water. In the fuzzy oil drop (FOD) model, this distribution is represented by the 3D Gauss function (3DG)...

Outer membrane proteins (OMPs) of Aeromonas hydrophila have a variety of functional roles in virulence and pathogenesis and represent promising targets for vaccine development. The main objective of this study was to develop an in-silico model of beta-barrel OMP present among the valid A. hydrophila pangenomes (n = 22). With a program named the β-barrel Outer Membrane Protein Predictor (BOMP), total beta-barrel OMPs (n = 3127) were predicted across 22 genomes with the estimated median number of 64 per genome...

Outer-membrane beta barrels (OMBBs) are found in the outer membrane of gram-negative bacteria and eukaryotic organelles. OMBBs fold as antiparallel β-sheets that close onto themselves, forming pores that traverse the membrane. Currently known structures include only one barrel, of 8 to 36 strands, per chain. The lack of multi-OMBB chains is surprising, as most OMBBs form oligomers, and some function only in this state. Using a combination of sensitive sequence comparison methods and coevolutionary analysis tools, we identify many proteins combining multiple beta barrels within a single chain; combinations that include eight-stranded barrels prevail...