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Journal of Molecular Biology Sep 2022Allosteric proteins transition between 'inactive' and 'active' states. In general, such proteins assume distinct conformational states at the level of secondary,... (Review)
Review
Allosteric proteins transition between 'inactive' and 'active' states. In general, such proteins assume distinct conformational states at the level of secondary, tertiary and/or quaternary structure. Different conformers of an allosteric protein can be antigenically dissimilar and induce antibodies with a highly distinctive specificities and neutralizing functional effects. Here we summarize studies on various functional types of monoclonal antibodies obtained against different allosteric conformers of the mannose-specific bacterial adhesin FimH - the most common cell attachment protein of Escherichia coli and other enterobacterial pathogens. Included are types of antibodies that activate the FimH function via interaction with ligand-induced binding sites or by wedging between domains as well as antibodies that inhibit FimH through orthosteric, parasteric, or novel dynasteric mechanisms. Understanding the molecular mechanism of antibody action against allosteric proteins provides insights on how to design antibodies with a desired functional effect, including those with neutralizing activity against bacterial and viral cell attachment proteins.
Topics: Adhesins, Escherichia coli; Allosteric Regulation; Antibodies, Neutralizing; Fimbriae Proteins; Protein Conformation
PubMed: 35798162
DOI: 10.1016/j.jmb.2022.167717 -
International Journal of Molecular... Dec 2022Bacteria express different types of hair-like proteinaceous appendages on their cell surface known as pili or fimbriae. These filamentous structures are primarily... (Review)
Review
Bacteria express different types of hair-like proteinaceous appendages on their cell surface known as pili or fimbriae. These filamentous structures are primarily involved in the adherence of bacteria to both abiotic and biotic surfaces for biofilm formation and/or virulence of non-pathogenic and pathogenic bacteria. In pathogenic bacteria, especially Gram-negative bacteria, fimbriae play a key role in bacteria-host interactions which are critical for bacterial invasion and infection. Fimbriae assembled by the Chaperone Usher pathway (CUP) are widespread within the , and their expression is tightly regulated by specific environmental stimuli. Genes essential for expression of CUP fimbriae are organised in small blocks/clusters, which are often located in proximity to other virulence genes on a pathogenicity island. Since these surface appendages play a crucial role in bacterial virulence, they have potential to be harnessed in vaccine development. This review covers the regulation of expression of CUP-assembled fimbriae in Gram-negative bacteria and uses selected examples to demonstrate both dedicated and global regulatory mechanisms.
Topics: Fimbriae, Bacterial; Gram-Negative Bacteria; Enterobacteriaceae; Gene Expression Regulation; Cell Membrane; Fimbriae Proteins
PubMed: 36613605
DOI: 10.3390/ijms24010161 -
The Journal of Biological Chemistry Aug 2012Over recent years, several examples of natural ribosomally synthesized circular proteins and peptides from diverse organisms have been described. They are a group of... (Review)
Review
Over recent years, several examples of natural ribosomally synthesized circular proteins and peptides from diverse organisms have been described. They are a group of proteins for which the precursors must be post-translationally modified to join the N and C termini with a peptide bond. This feature appears to confer a range of potential advantages because these proteins show increased resistance to proteases and higher thermodynamic stability, both of which improve their biological activity. They are produced by prokaryotic and eukaryotic organisms and show diverse biological activities, related mostly to a self-defense or competition mechanism of the producer organisms, with the only exception being the circular pilins. This minireview highlights ribosomally synthesized circular proteins produced by members of the domain Bacteria: circular bacteriocins, cyanobactins, and circular pilins. We pay special attention to the genetic organization of the biosynthetic machinery of these molecules, the role of circularization, and the differences in the possible circularization mechanisms.
Topics: Bacterial Proteins; Bacteriocins; Fimbriae Proteins; Models, Molecular; Protein Conformation
PubMed: 22700986
DOI: 10.1074/jbc.R112.354688 -
IUBMB Life Jul 2015Pilins or fimbrilins are a class of proteins found in bacterial surface pilus, a hair-like surface appendage. Both the Gram-negative and -positive bacteria produce... (Review)
Review
Pilins or fimbrilins are a class of proteins found in bacterial surface pilus, a hair-like surface appendage. Both the Gram-negative and -positive bacteria produce pilins to assemble pili on their cell-surface for different purposes including adherence, twitching motility, conjugation, immunomodulation, biofilm formation, and electron transfer. Immunogenic properties of the pilins make them attractive vaccine candidates. The polymerized pilins play a key role in the initiation of host adhesion, which is a critical step for bacterial colonization and infection. Because of their key role in adhesion and exposure on the cell surface, targeting the pilins-mediated adhesion (anti-adhesion therapy) is also seen as a promising alternative approach for preventing and treating bacterial infections, one that may overcome their ever-increasing repertoires of resistance mechanisms. Individual pilins interact with each other non-covalently to assemble the pilus fiber with the help of associated proteins like chaperones and Usher in Gram-negative bacteria. In contrast, the pilins in Gram-positive bacteria often connect with each other covalently, with the help of sortases. Certain unique structural features present on the pilins distinguish them from one another across different bacterial strains, and these dictate their cellular targets and functions. While the structure of pilins has been extensively studied in Gram-negative pathogenic bacteria, the pilins in Gram-positive pathogenic bacteria have been in only during the last decade. Recently, the discovery of pilins in non-pathogenic bacteria, such as Lactobacillus rhamnosus GG, has received great attention, though traditionally the attention was on pathogenic bacteria. This review summarizes and discusses the current structural knowledge of pilins in Gram-positive bacteria with emphasis on those pilins which are sortase substrates.
Topics: Amino Acid Motifs; Amino Acid Sequence; Conserved Sequence; Fimbriae Proteins; Fimbriae, Bacterial; Gram-Positive Bacteria; Protein Structure, Tertiary
PubMed: 26178080
DOI: 10.1002/iub.1400 -
Frontiers in Cellular and Infection... 2023The pilus is an extracellular structural part that can be detected in some () isolates (type I pili are found in approximately 30% of strains, while type II pili are... (Review)
Review
The pilus is an extracellular structural part that can be detected in some () isolates (type I pili are found in approximately 30% of strains, while type II pili are found in approximately 20%). It is anchored to the cell wall by LPXTG-like motifs on the peptidoglycan. Two kinds of pili have been discovered, namely, pilus-1 and pilus-2. The former is encoded by pilus islet 1 (PI-1) and is a polymer formed by the protein subunits RrgA, RrgB and RrgC. The latter is encoded by pilus islet 2 (PI-2) and is a polymer composed mainly of the structural protein PitB. Although pili are not necessary for the survival of , they serve as the structural basis and as virulence factors that mediate the adhesion of bacteria to host cells and play a direct role in promoting the adhesion, colonization and pathogenesis of . In addition, as candidate antigens for protein vaccines, pili have promising potential for use in vaccines with combined immunization strategies. Given the current understanding of the pili of regarding the genes, proteins, structure, biological function and epidemiological relationship with serotypes, combined with the immunoprotective efficacy of pilins as protein candidates for vaccines, we here systematically describe the research status and prospects of pili and provide new ideas for subsequent vaccine research and development.
Topics: Bacterial Proteins; Streptococcus pneumoniae; Fimbriae, Bacterial; Fimbriae Proteins; Vaccines; Polymers
PubMed: 37799336
DOI: 10.3389/fcimb.2023.1270848 -
Medical Microbiology and Immunology Jun 2020Type IV pili are versatile and highly flexible fibers formed on the surface of many Gram-negative and Gram-positive bacteria. Virulence and infection rate of several... (Review)
Review
Type IV pili are versatile and highly flexible fibers formed on the surface of many Gram-negative and Gram-positive bacteria. Virulence and infection rate of several pathogenic bacteria, such as Neisseria meningitidis and Pseudomonas aeruginosa, are strongly dependent on the presence of pili as they facilitate the adhesion of the bacteria to the host cell. Disruption of the interactions between the pili and the host cells by targeting proteins involved in this interaction could, therefore, be a treatment strategy. A type IV pilus is primarily composed of multiple copies of protein subunits called major pilins. Additional proteins, called minor pilins, are present in lower abundance, but are essential for the assembly of the pilus or for its specific functions. One class of minor pilins is required to initiate the formation of pili, and may form a complex similar to that identified in the related type II secretion system. Other, species-specific minor pilins in the type IV pilus system have been shown to promote additional functions such as DNA binding, aggregation and adherence. Here, we will review the structure and the function of the minor pilins from type IV pili.
Topics: Bacterial Adhesion; Fimbriae Proteins; Fimbriae, Bacterial; Host Microbial Interactions; Models, Molecular; Protein Conformation; Protein Multimerization; Virulence
PubMed: 31784891
DOI: 10.1007/s00430-019-00642-5 -
Microbiology Spectrum Mar 2019Type IV pilus (T4P)-like systems have been identified in almost every major phylum of prokaryotic life. They include the type IVa pilus (T4aP), type II secretion system... (Review)
Review
Type IV pilus (T4P)-like systems have been identified in almost every major phylum of prokaryotic life. They include the type IVa pilus (T4aP), type II secretion system (T2SS), type IVb pilus (T4bP), Tad/Flp pilus, Com pilus, and archaeal flagellum (archaellum). These systems are used for adhesion, natural competence, phage adsorption, folded-protein secretion, surface sensing, swimming motility, and twitching motility. The T4aP allows for all of these functions except swimming and is therefore a good model system for understanding T4P-like systems. Recent structural analyses have revolutionized our understanding of how the T4aP machinery assembles and functions. Here we review the structure and function of the T4aP.
Topics: Fimbriae Proteins; Fimbriae, Bacterial; Flagella; Protein Transport; Type II Secretion Systems
PubMed: 30825300
DOI: 10.1128/microbiolspec.PSIB-0006-2018 -
MBio Jun 2022
Topics: Electron Transport; Fimbriae Proteins; Fimbriae, Bacterial; Geobacter; Nanowires; Oxidation-Reduction
PubMed: 35642973
DOI: 10.1128/mbio.00850-22 -
Frontiers in Cellular and Infection... 2020is one of the most diverse and successful pathogens, representing a species with >2,600 serovars with a variety of adaptations that enable colonization and infection of... (Review)
Review
is one of the most diverse and successful pathogens, representing a species with >2,600 serovars with a variety of adaptations that enable colonization and infection of a wide range of hosts. Fimbriae, thin hair-like projections that cover the surface of , are thought to be the primary organelles that mediate 's interaction with, and adherence to, the host intestinal epithelium, representing an important step in the infection process. The recent expansion in genome sequencing efforts has enabled the discovery of novel fimbriae, thereby providing new perspectives on fimbrial diversity and distribution among a broad number of serovars. In this review, we provide an updated overview of the evolutionary events that shaped the chaperone-usher fimbriome in light of recent phylogenetic studies describing the population structure of . Furthermore, we discuss the complexities of the chaperone-usher fimbriae-mediated host-pathogen interactions and the apparent redundant roles of chaperone-usher fimbriae in host and tissue tropism.
Topics: Fimbriae Proteins; Fimbriae, Bacterial; Molecular Chaperones; Phylogeny; Salmonella; Tropism
PubMed: 33614531
DOI: 10.3389/fcimb.2020.628043 -
Microbiology and Molecular Biology... Dec 2012Type IV pili (T4P) are multifunctional protein fibers produced on the surfaces of a wide variety of bacteria and archaea. The major subunit of T4P is the type IV pilin,... (Review)
Review
Type IV pili (T4P) are multifunctional protein fibers produced on the surfaces of a wide variety of bacteria and archaea. The major subunit of T4P is the type IV pilin, and structurally related proteins are found as components of the type II secretion (T2S) system, where they are called pseudopilins; of DNA uptake/competence systems in both Gram-negative and Gram-positive species; and of flagella, pili, and sugar-binding systems in the archaea. This broad distribution of a single protein family implies both a common evolutionary origin and a highly adaptable functional plan. The type IV pilin is a remarkably versatile architectural module that has been adopted widely for a variety of functions, including motility, attachment to chemically diverse surfaces, electrical conductance, acquisition of DNA, and secretion of a broad range of structurally distinct protein substrates. In this review, we consider recent advances in this research area, from structural revelations to insights into diversity, posttranslational modifications, regulation, and function.
Topics: Bacterial Physiological Phenomena; Biofilms; Conjugation, Genetic; Fimbriae Proteins; Fimbriae, Bacterial; Genetic Variation; Host-Pathogen Interactions; Pili, Sex; Protein Structure, Secondary; Protein Subunits; Signal Transduction; Transcription, Genetic
PubMed: 23204365
DOI: 10.1128/MMBR.00035-12