Structure-function relationships of antimicrobial peptides

1998 ◽  
Vol 76 (2-3) ◽  
pp. 235-246 ◽  
Author(s):  
Peter M Hwang ◽  
Hans J Vogel
Keyword(s):  
Antimicrobial Peptides ◽  
Hemolytic Activity ◽  
Mammalian Cells ◽  
Rational Design ◽  
Current Knowledge ◽  
Membrane Binding ◽  
Three Dimensional ◽  
Exact Nature ◽  
Additional Information ◽  
Bacteria And Fungi

Antimicrobial peptides are ubiquitously produced throughout nature. Many of these relatively short peptides (6-50 residues) are lethal towards bacteria and fungi, yet they display minimal toxicity towards mammalian cells. All of the peptides are highly cationic and hydrophobic. It is widely believed that they act through nonspecific binding to biological membranes, even though the exact nature of these interactions is presently unclear. High-resolution nuclear magnetic resonance (NMR) has contributed greatly to knowledge in this field, providing insight about peptide structure in aqueous solution, in organic cosolvents, and in micellar systems. Solid-state NMR can provide additional information about peptide-membrane binding. Here we review our current knowledge about the structure of antimicrobial peptides. We also discuss studies pertaining to the mechanism of action. Despite the different three-dimensional structural motifs of the various classes, they all have similar amphiphilic surfaces that are well-suited for membrane binding. Many antimicrobial peptides bind in a membrane-parallel orientation, interacting only with one face of the bilayer. This may be sufficient for antimicrobial action. At higher concentrations, peptides and phospholipids translocate to form multimeric transmembrane channels that seem to contribute to the peptide's hemolytic activity. An understanding of the key features of the secondary and tertiary structures of the antimicrobial peptides and their effects on bactericidal and hemolytic activity can aid the rational design of improved analogs for clinical use.Key words: structure, antimicrobial peptide, NMR, membrane, hemolytic.

scholarly journals Multiple Parameters Beyond Lipid Binding Affinity Drive Cytotoxicity of Cholesterol-Dependent Cytolysins

Toxins ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 1 ◽  
Author(s):  
Sucharit Ray ◽  
Roshan Thapa ◽  
Peter Keyel
Keyword(s):  
Cell Death ◽  
Binding Affinity ◽  
Hemolytic Activity ◽  
Mammalian Cells ◽  
Pathogenic Bacteria ◽  
Calcium Influx ◽  
Membrane Binding ◽  
Lipid Binding ◽  
Membrane Repair ◽  
Death Kinetics

The largest superfamily of bacterial virulence factors is pore-forming toxins (PFTs). PFTs are secreted by both pathogenic and non-pathogenic bacteria. PFTs sometimes kill or induce pro-pathogen signaling in mammalian cells, all primarily through plasma membrane perforation, though the parameters that determine these outcomes are unclear. Membrane binding, calcium influx, pore size, and membrane repair are factors that influence PFT cytotoxicity. To test the contribution of membrane binding to cytotoxicity and repair, we compared the closely related, similarly-sized PFTs Perfringolysin O (PFO) from Clostridium perfringens and Streptolysin O (SLO) from Streptococcus pyogenes. Cell death kinetics for PFO and SLO were different because PFO increased in cytotoxicity over time. We introduced known L3 loop mutations that swap binding affinity between toxins and measured hemolytic activity, nucleated cell death kinetics and membrane repair using viability assays, and live cell imaging. Altered hemolytic activity was directly proportional to toxin binding affinity. In contrast, L3 loop alterations reduced nucleated cell death, and they had limited effects on cytotoxicity kinetics and membrane repair. This suggests other toxin structural features, like oligomerization, drives these parameters. Overall, these findings suggest that repair mechanisms and toxin oligomerization add constraints beyond membrane binding on toxin evolution and activity against nucleated cells.

Cryptic Antimicrobial Peptides: Identification Methods and Current Knowledge of their Immunomodulatory Properties

2018 ◽  
Vol 24 (10) ◽  
pp. 1054-1066 ◽  
Author(s):  
Elio Pizzo ◽  
Valeria Cafaro ◽  
Alberto Di Donato ◽  
Eugenio Notomista
Keyword(s):  
Antimicrobial Peptides ◽  
Mechanism Of Action ◽  
Rational Design ◽  
Wound Repair ◽  
Current Knowledge ◽  
Lipoteichoic Acid ◽  
Attractive Alternative ◽  
Bacterial Membranes ◽  
Evolutionarily Conserved ◽  
Bacterial Surfaces

Cationic antimicrobial peptides (CAMPs), also known as host defence peptides (HDPs), are essential evolutionarily conserved components of innate immunity, constitutively or inducibly expressed in response to invasion by pathogens. In addition to a direct antimicrobial action, they are able to synergistically operate with other defence molecules to combat infection by neutralization of endotoxins, chemokine-like activities, induction of angiogenesis and wound repair. The importance of CAMPs has been highlighted in animal models and supported by observations in patient studies. CAMPs are attractive alternative candidates to antibiotic treatment, because they offer several advantages over the currently used drugs, moreover, knowledge on these peptides, especially regarding the intertwinement between their structure, function and mechanism of action, could be applied in the rational design of antimicrobial/anti-inflammatory/wound healing enhancing drugs. CAMPs combat pathogens by targeting bacterial membranes and essential membrane-related functions, and, in some cases, also target intracellular components. Despite differences in their size and sequence, many of them share a net positive charge and fold into amphipathic structures after contact with bacterial surfaces or endotoxins like lipopolysaccharides and lipoteichoic acid. Due to their peculiar mechanism, acquisition of resistance towards these peptides would be difficult for the bacteria. Very interestingly it has been demonstrated that several proteins, including proteins apparently not involved in immunity, can behave as sources of CAMPs hidden in their primary structures and released by the action of host and/or bacterial proteases. The existence of these “cryptic CAMPs” suggests that the panel of antimicrobial peptides present in higher eukaryotes and the variety of functions they perform could be much wider and more complex than previously suspected. This review focuses on source, structure and mechanism of action of cryptic CAMPs, with special attention to their immunomodulatory functions.

scholarly journals DNA Replication Timing Enters the Single-Cell Era

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 221 ◽  
Author(s):  
Ichiro Hiratani ◽  
Saori Takahashi
Keyword(s):  
Dna Replication ◽  
Single Cell ◽  
Cell Population ◽  
Mammalian Cells ◽  
Current Knowledge ◽  
Three Dimensional ◽  
Replication Timing ◽  
3D Genome ◽  
Population Analyses ◽  
Dna Replication Timing

In mammalian cells, DNA replication timing is controlled at the level of megabase (Mb)-sized chromosomal domains and correlates well with transcription, chromatin structure, and three-dimensional (3D) genome organization. Because of these properties, DNA replication timing is an excellent entry point to explore genome regulation at various levels and a variety of studies have been carried out over the years. However, DNA replication timing studies traditionally required at least tens of thousands of cells, and it was unclear whether the replication domains detected by cell population analyses were preserved at the single-cell level. Recently, single-cell DNA replication profiling methods became available, which revealed that the Mb-sized replication domains detected by cell population analyses were actually well preserved in individual cells. In this article, we provide a brief overview of our current knowledge on DNA replication timing regulation in mammals based on cell population studies, outline the findings from single-cell DNA replication profiling, and discuss future directions and challenges.

Macroorganisation and flexibility of thylakoid membranes

2019 ◽  
Vol 476 (20) ◽  
pp. 2981-3018 ◽  
Author(s):  
Petar H. Lambrev ◽  
Parveen Akhtar
Keyword(s):  
Light Harvesting ◽  
Current Knowledge ◽  
Three Dimensional ◽  
Photosynthetic Apparatus ◽  
Dynamic Responses ◽  
State Transitions ◽  
Photochemical Quenching ◽  
Light Harvesting Complex ◽  
Complex Ii ◽  
Light Harvesting Complex Ii

Abstract The light reactions of photosynthesis are hosted and regulated by the chloroplast thylakoid membrane (TM) — the central structural component of the photosynthetic apparatus of plants and algae. The two-dimensional and three-dimensional arrangement of the lipid–protein assemblies, aka macroorganisation, and its dynamic responses to the fluctuating physiological environment, aka flexibility, are the subject of this review. An emphasis is given on the information obtainable by spectroscopic approaches, especially circular dichroism (CD). We briefly summarise the current knowledge of the composition and three-dimensional architecture of the granal TMs in plants and the supramolecular organisation of Photosystem II and light-harvesting complex II therein. We next acquaint the non-specialist reader with the fundamentals of CD spectroscopy, recent advances such as anisotropic CD, and applications for studying the structure and macroorganisation of photosynthetic complexes and membranes. Special attention is given to the structural and functional flexibility of light-harvesting complex II in vitro as revealed by CD and fluorescence spectroscopy. We give an account of the dynamic changes in membrane macroorganisation associated with the light-adaptation of the photosynthetic apparatus and the regulation of the excitation energy flow by state transitions and non-photochemical quenching.

scholarly journals Picosecond time-resolved photon antibunching measures nanoscale exciton motion and the true number of chromophores

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gordon J. Hedley ◽  
Tim Schröder ◽  
Florian Steiner ◽  
Theresa Eder ◽  
Felix J. Hofmann ◽  
...  
Keyword(s):  
Rational Design ◽  
Three Dimensional ◽  
Dna Origami ◽  
Fluorescent Nanoparticles ◽  
Time Resolved ◽  
Exciton Diffusion ◽  
Polymer Aggregates ◽  
True Number ◽  
Particle Level ◽  
Photon Antibunching

AbstractThe particle-like nature of light becomes evident in the photon statistics of fluorescence from single quantum systems as photon antibunching. In multichromophoric systems, exciton diffusion and subsequent annihilation occurs. These processes also yield photon antibunching but cannot be interpreted reliably. Here we develop picosecond time-resolved antibunching to identify and decode such processes. We use this method to measure the true number of chromophores on well-defined multichromophoric DNA-origami structures, and precisely determine the distance-dependent rates of annihilation between excitons. Further, this allows us to measure exciton diffusion in mesoscopic H- and J-type conjugated-polymer aggregates. We distinguish between one-dimensional intra-chain and three-dimensional inter-chain exciton diffusion at different times after excitation and determine the disorder-dependent diffusion lengths. Our method provides a powerful lens through which excitons can be studied at the single-particle level, enabling the rational design of improved excitonic probes such as ultra-bright fluorescent nanoparticles and materials for optoelectronic devices.

scholarly journals Plant antimicrobial peptides: structures, functions, and applications

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Junpeng Li ◽  
Shuping Hu ◽  
Wei Jian ◽  
Chengjian Xie ◽  
Xingyong Yang
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Agricultural Production ◽  
Food Additives ◽  
Antimicrobial Activities ◽  
Gram Positive Bacteria ◽  
Potential Applications ◽  
Potential Applicability ◽  
Bacteria And Fungi ◽  
Positively Charged

AbstractAntimicrobial peptides (AMPs) are a class of short, usually positively charged polypeptides that exist in humans, animals, and plants. Considering the increasing number of drug-resistant pathogens, the antimicrobial activity of AMPs has attracted much attention. AMPs with broad-spectrum antimicrobial activity against many gram-positive bacteria, gram-negative bacteria, and fungi are an important defensive barrier against pathogens for many organisms. With continuing research, many other physiological functions of plant AMPs have been found in addition to their antimicrobial roles, such as regulating plant growth and development and treating many diseases with high efficacy. The potential applicability of plant AMPs in agricultural production, as food additives and disease treatments, has garnered much interest. This review focuses on the types of plant AMPs, their mechanisms of action, the parameters affecting the antimicrobial activities of AMPs, and their potential applications in agricultural production, the food industry, breeding industry, and medical field.

scholarly journals Flowering plant embryos: How did we end up here?

2021 ◽  
Author(s):  
Stefan A. Rensing ◽  
Dolf Weijers
Keyword(s):  
Current Knowledge ◽  
General Structure ◽  
Three Dimensional ◽  
Flowering Plants ◽  
Flowering Plant ◽  
Adult Plant ◽  
Ancestral State ◽  
Evolutionary Trajectory ◽  
Current State ◽  
Plant Embryo

AbstractThe seeds of flowering plants are sexually produced propagules that ensure dispersal and resilience of the next generation. Seeds harbor embryos, three dimensional structures that are often miniatures of the adult plant in terms of general structure and primordial organs. In addition, embryos contain the meristems that give rise to post-embryonically generated structures. However common, flowering plant embryos are an evolutionary derived state. Flowering plants are part of a much larger group of embryo-bearing plants, aptly termed Embryophyta. A key question is what evolutionary trajectory led to the emergence of flowering plant embryos. In this opinion, we deconstruct the flowering plant embryo and describe the current state of knowledge of embryos in other plant lineages. While we are far yet from understanding the ancestral state of plant embryogenesis, we argue what current knowledge may suggest and how the knowledge gaps may be closed.

Sign in / Sign up

Export Citation Format

Share Document