A5012403259- Lipid Membrane Structure and Behavior
- Advanced Electron Microscopy Techniques and Applications
- Bacterial Genetics and Biotechnology
- Nanopore and Nanochannel Transport Studies
- Enzyme Structure and Function
- Alzheimer's disease research and treatments
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Urinary Tract Infections Management
- Ion channel regulation and function
- Spectroscopy and Quantum Chemical Studies
- Steroid Chemistry and Biochemistry
- Peptidase Inhibition and Analysis
- Microbial Metabolism and Applications
- Gut microbiota and health
- Virology and Viral Diseases
- Plant-based Medicinal Research
- Viral Infections and Vectors
- RNA Interference and Gene Delivery
- Oral microbiology and periodontitis research
- Antibiotic Resistance in Bacteria
- Photosynthetic Processes and Mechanisms
- Clostridium difficile and Clostridium perfringens research
- HIV Research and Treatment
- Mosquito-borne diseases and control
Forschungszentrum Jülich
2018-2024
Duke University
2024
Constructor University
2015-2020
University of Bremen
2015
Abstract The human cathelicidin LL-37 serves a critical role in the innate immune system defending bacterial infections. can interact with molecules of cell wall and perforate cytoplasmic membranes resulting death. To test interactions components we crystallized presence detergents obtained structure narrow tetrameric channel strongly charged core. formation tetramer was further studied by cross-linking lipids. Using planar lipid small but defined conductivity this could be demonstrated....
Abstract HIV-1 envelope glycoproteins (Envs) of most primary strains exist in closed conformation and infrequently sample open states, limiting access to internal epitopes. Thus, immunogen design aims mimic the Env as preferred target for eliciting broadly neutralizing antibodies (bnAbs). Here we identify incompletely conformations 6 out 13 transmitted/founder (T/F) that are sensitive recognize epitopes typically exposed on Envs. A 3.6 Å cryo-electron microscopy structure unliganded, T/F...
The Henipavirus genus is quickly expanding into new animal hosts and geographic locations. This study compares the structure antigenicity of Langya virus fusion protein to other henipaviruses, which have important vaccine therapeutic development implications. Furthermore, proposes a mechanism explain early steps initiation process that can be more broadly applied Paramyxoviridae family.
Chitin, an insoluble polymer of N-acetylglucosamine, is one the most abundant biopolymers on Earth. By degrading chitin, chitinolytic bacteria such as Vibrio harveyi are critical for chitin recycling and maintenance carbon nitrogen cycles in world's oceans. A decisive step degradation uptake chito-oligosaccharides by outer membrane protein channel named chitoporin (ChiP). Here, we report X-ray crystal structures ChiP from V. presence absence chito-oligosaccharides. Structures without bound...
The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound protein protein/nucleic-acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published were selected as targets: E. coli beta-galactosidase with inhibitor, SARS-CoV-2 RNA-dependent RNA polymerase covalently nucleotide analog, ion channel ORF3a lipid. Sixty-one models submitted from 17 independent research...
A Brownian dynamics (BD) approach including explicit atoms called BRODEA is presented to model ion permeation and molecule translocation across a nanopore confinement. This generalizes our previous hybrid molecular dynamics–Brownian framework (J. Chem. Theory Comput. 2016, 12, 2401) by incorporating widespread enhanced set of simulation schemes based on several boundary conditions electrostatic models, as well temperature accelerated method for sampling free energy surfaces determining...
Protein-lipopolysaccharide (LPS) interactions play an important role in providing a stable outer membrane to Gram-negative bacteria. However, the LPS molecules are highly viscous, and sampling motions is thus challenging on microsecond time scale simulations. To this end, we introduce new protocol randomly allow self-assemble around protein thereby reduce starting bias Here present all-atom molecular dynamics simulations of OmpE36 porin model which sum up simulation more than 20 μs identify...
All-atom molecular dynamics simulations have a long history of applications studying ion and substrate permeation across biological artificial pores. While offering unprecedented insights into the underpinning transport processes, MD are limited in time-scales ability to simulate physiological membrane potentials or asymmetric salt solutions require substantial computational power. several approaches circumvent all these limitations were developed, Brownian remain an attractive option field....
Abstract HIV-1 envelope glycoproteins (Envs) mediate viral entry and are the sole target of neutralizing antibodies. Envs most primary strains exist in a closed conformation occasionally sample more open states. Thus, current knowledge guides immunogen design to mimic Env as preferred for eliciting broadly antibodies (bnAbs) block entry. Here we show that Env-preferred conformations 6 out 13 (46%) transmitted/founder (T/F) tested incompletely closed. As result, these T/Fs into cells is...
The OccK protein subfamily located in the outer membrane of Pseudomonas aeruginosa contains dynamic channels with several conformational states that range from open to closed forms. molecular determinants contribute diverse gating have, however, remained elusive so far. Performing dynamics (MD) simulations on OccK5 (OpdH) as an example, local fluctuations loop L7 mediated by a single residue were identified effectively gate channel. features this studied single-channel electrophysiology and...
The outer membrane (OM) of Gram-negative bacteria is a unique asymmetric lipid bilayer containing lipopolysaccharides (LPS) in the leaflet and phospholipids inner leaflet. Due to lack porins with large pores, substrate-specific proteins play crucial role uptake small molecules Pseudomonas aeruginosa. In this study, we report influences OM compositions on ion permeation properties OccK5 (also known as OpdH), such selectivity diffusion constants, using all-atom molecular dynamics simulations....
Molecular simulations have been performed on the pore OpdK elucidating molecular details of ion conductance and a possible gating mechanism.
The environmental coupling of the phycobiliprotein antenna complex PE555 and its excitonic energy transfer mechanisms are studied in detail. Molecular dynamics simulations were performed followed by calculations vertical transition energies along classical ground-state trajectory. To this end, distributions levels for found to be similar those PE545 despite clear differences respective protein structures. In two αβ monomers rotated ∼73° compared structure leading a water filled channel....
Corynebacterium urealyticum, a pathogenic, multidrug resistant member of the mycolata, is known as causative agent urinary tract infections although it bacterium skin flora. This pathogenic shares with mycolata property having an unusual cell envelope composition and architecture, typical for genus Corynebacterium. The wall members contains channel-forming proteins uptake solutes. In this study, we provide novel information on identification characterization pore-forming protein in C....
Abstract A critical role of the hormone islet amyloid polypeptide (IAPP) is vividly discussed for Type 2 Diabetes (T2D), where deposits in pancreatic islets consisting fibrillar IAPP have been associated with beta cell loss. Here, we applied cryo-electron microscopy to elucidate structure fibrils prepared at physiological pH and reconstructed densities three dominant polymorphs. An atomic model main polymorph comprising residues 13 – 37 a density map 4.2 Å resolution reveals two S-shaped,...
Abstract Porphyromonas gingivalis , an asaccharolytic Bacteroidetes is a keystone pathogen in human periodontitis that may also contribute to the development of other chronic inflammatory diseases, such as rheumatoid arthritis, cardiovascular disease and Alzheimer’s disease. P. utilizes protease-generated peptides derived from extracellular proteins for growth, but how those enter cell not clear. Here we identify RagAB outer membrane importer peptides. X-ray crystal structures show...