Dataset Information

Refinement of OprH-LPS Interactions by Molecular Simulations.

ABSTRACT: The outer membrane (OM) of Gram-negative bacteria is composed of lipopolysaccharide (LPS) in the outer leaflet and phospholipids in the inner leaflet. The outer membrane protein H (OprH) of Pseudomonas aeruginosa provides an increased stability to the OMs by directly interacting with LPS. Here we report the influence of various P. aeruginosa and, for comparison, Escherichia coli LPS environments on the physical properties of the OMs and OprH using all-atom molecular dynamics simulations. The simulations reveal that although the P. aeruginosa OMs are thinner hydrophobic bilayers than the E. coli OMs, which is expected from the difference in the acyl chain length of their lipid A, this effect is almost imperceptible around OprH due to a dynamically adjusted hydrophobic match between OprH and the OM. The structure and dynamics of the extracellular loops of OprH show distinct behaviors in different LPS environments. Including the O-antigen greatly reduces the flexibility of the OprH loops and increases the interactions between these loops and LPS. Furthermore, our study shows that the interactions between OprH and LPS mainly depend on the secondary structure of OprH and the chemical structure of LPS, resulting in distinctive patterns in different LPS environments.

SUBMITTER: Lee J

PROVIDER: S-EPMC5266143 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Refinement of OprH-LPS Interactions by Molecular Simulations.

Lee Joonseong J Patel Dhilon S DS Kucharska Iga I Tamm Lukas K LK Im Wonpil W

Biophysical journal 20170101 2

The outer membrane (OM) of Gram-negative bacteria is composed of lipopolysaccharide (LPS) in the outer leaflet and phospholipids in the inner leaflet. The outer membrane protein H (OprH) of Pseudomonas aeruginosa provides an increased stability to the OMs by directly interacting with LPS. Here we report the influence of various P. aeruginosa and, for comparison, Escherichia coli LPS environments on the physical properties of the OMs and OprH using all-atom molecular dynamics simulations. The sim ...[more]

PMID: 28122220

Similar Datasets

Project description:The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with the consensus model of the resting state VSD and the spin-spin distance histograms from ESR/DEER experiments on T4 lysozyme are accurately reproduced.

Dataset Information

Refinement of OprH-LPS Interactions by Molecular Simulations.

Publications

Refinement of OprH-LPS Interactions by Molecular Simulations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets