Dataset Information

H/D exchange centroid monitoring is insufficient to show differences in the behavior of protein states.

ABSTRACT: Differential hydrogen/deuterium exchange (H/DX) coupled with mass spectrometry (H/DX-MS) offers a rapid and sensitive characterization of changes in proteins following perturbations induced by changes in folding, ligand binding, oligomerization, and modification. The characterization of H/DX rates by software tools and automated data processing often relies on the centroid mass calculation and, thereby, the deuterium distribution in the mass spectra is neglected. Here we present an example demonstrating the clear limitation of using only a centroid approach to characterize the H/DX rate, in which the change in protein is not reflected as the difference in deuterium uptake based on centroid calculation.

SUBMITTER: Zhang J

PROVIDER: S-EPMC3594389 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

H/D exchange centroid monitoring is insufficient to show differences in the behavior of protein states.

Zhang Jun J Ramachandran Pradeep P Kumar Rajiv R Gross Michael L ML

Journal of the American Society for Mass Spectrometry 20130209 3

Differential hydrogen/deuterium exchange (H/DX) coupled with mass spectrometry (H/DX-MS) offers a rapid and sensitive characterization of changes in proteins following perturbations induced by changes in folding, ligand binding, oligomerization, and modification. The characterization of H/DX rates by software tools and automated data processing often relies on the centroid mass calculation and, thereby, the deuterium distribution in the mass spectra is neglected. Here we present an example demon ...[more]

PMID: 23397137

Similar Datasets

Project description:BackgroundNeurofibromatosis type 1 (NF1) is an inherited neurocutaneous disorder associated with neurodevelopmental disorders including autism spectrum disorder (ASD). This condition has been associated with an increase of gamma-aminobutyric acid (GABA) neurotransmission and, consequently, an excitation/inhibition imbalance associated with autistic-like behavior in both human and animal models. Here, we explored the influence of biological sex in the GABAergic system and behavioral alterations induced by the Nf1+/- mutation in a murine model.MethodsJuvenile male and female Nf1+/- mice and their wild-type (WT) littermates were used. Hippocampus size was assessed by conventional toluidine blue staining and structural magnetic resonance imaging (MRI). Hippocampal GABA and glutamate levels were determined by magnetic resonance spectroscopy (MRS), which was complemented by western blot for the GABA(A) receptor. Behavioral evaluation of on anxiety, memory, social communication, and repetitive behavior was performed.ResultsWe found that juvenile female Nf1+/- mice exhibited increased hippocampal GABA levels. Moreover, mutant female displays a more prominent anxious-like behavior together with better memory performance and social behavior. On the other hand, juvenile Nf1+/- male mice showed increased hippocampal volume and thickness, with a decrease in GABA(A) receptor levels. We observed that mutant males had higher tendency for repetitive behavior.ConclusionsOur results suggested a sexually dimorphic impact of Nf1+/- mutation in hippocampal neurochemistry, and autistic-like behaviors. For the first time, we identified a "camouflaging"-type behavior in females of an animal model of ASD, which masked their autistic traits. Accordingly, like observed in human disorder, in this animal model of ASD, females show larger anxiety levels but better executive functions and production of normative social patterns, together with an imbalance of inhibition/excitation ratio. Contrary, males have more externalizing disorders, such as hyperactivity and repetitive behaviors, with memory deficits. The ability of females to camouflage their autistic traits creates a phenotypic evaluation challenge that mimics the diagnosis difficulty observed in humans. Thus, we propose the study of the Nf1+/- mouse model to better understand the sexual dimorphisms of ASD phenotypes and to create better diagnostic tools.

Dataset Information

H/D exchange centroid monitoring is insufficient to show differences in the behavior of protein states.

Publications

H/D exchange centroid monitoring is insufficient to show differences in the behavior of protein states.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets