Dataset Information

Effects of Detergent on ?-Synuclein Structure. A Native MS-Ion Mobility Study.

ABSTRACT: The intrinsically disordered protein ?-synuclein plays a major role in Parkinson's disease. The protein can oligomerize resulting in the formation of various aggregated species in neuronal cells, leading to neurodegeneration. The interaction of ?-synuclein with biological cell membranes plays an important role for specific functions of ?-synuclein monomers, e.g., in neurotransmitter release. Using different types of detergents to mimic lipid molecules present in biological membranes, including the presence of Ca2+ ions as an important structural factor, we aimed to gain an understanding of how ?-synuclein interacts with membrane models and how this affects the protein conformation and potential oligomerization. We investigated detergent binding stoichiometry, affinity and conformational changes of ?-synuclein taking detergent concentration, different detergent structures and charges into account. With native nano-electrospray ionization ion mobility-mass spectrometry, we were able to detect unique conformational patterns resulting from binding of specific detergents to ?-synuclein. Our data demonstrate that ?-synuclein monomers can interact with detergent molecules irrespective of their charge, that protein-micelle interactions occur and that micelle properties are an important factor.

SUBMITTER: Moons R

PROVIDER: S-EPMC7660655 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of Detergent on α-Synuclein Structure. A Native MS-Ion Mobility Study.

Moons Rani R van der Wekken-de Bruijne Renate R Maudsley Stuart S Lemière Filip F Lambeir Anne-Marie AM Sobott Frank F

International journal of molecular sciences 20201023 21

The intrinsically disordered protein α-synuclein plays a major role in Parkinson's disease. The protein can oligomerize resulting in the formation of various aggregated species in neuronal cells, leading to neurodegeneration. The interaction of α-synuclein with biological cell membranes plays an important role for specific functions of α-synuclein monomers, e.g., in neurotransmitter release. Using different types of detergents to mimic lipid molecules present in biological membranes, including t ...[more]

PMID: 33114222

Similar Datasets

Project description:IntroductionIon mobility-mass spectrometry (IM-MS) is an emerging technique in the -omics fields that has broad potential applicability to the clinical lab. As a rapid, gas-phase structure-based separation technique, IM-MS offers promise in isomer separations and can be easily combined with existing LC-MS methods (i.e., LC-IM-MS). Several experimental conditions, including analyte cation adducts and drift composition further provide a means to tune separations for global and/or targeted applications.ObjectivesThe primary objective of this study was to demonstrate the utility of IM-MS under a range of experimental conditions for detection of glucocorticoids, and specifically for the separation of several isomeric pairs.MethodsLC-IM-MS was used to characterize 16 glucocorticoids including three isomer pairs: cortisone/prednisolone, betamethasone/dexamethasone, and flunisolide/triamcinolone acetonide. Collision cross section (CCS) values were measured for all common adducts (e.g., protonated and sodiated) using both step-field and single-field methods. Alternative alkali, alkaline earth, and transition metals were introduced, such that their adducts could also be measured. Finally, four different drift gases (helium, nitrogen, argon, and carbon dioxide) were compared for their relative separation capability.ResultsLC-IM-MS offered a robust, multidimensional separation technique that allowed for the 16 glucocorticoids to be analyzed and separated in three-dimensions (retention time, CCS, and m/z). Despite the relatively modest resolution of isomer pairs under standard conditions (i.e., nitrogen drift gas, sodiated ions, etc.), improvements were observed for alkaline earth and transition metals (notable barium adducts) and in carbon dioxide drift gas.ConclusionIn summary, LC-IM-MS offers potential as a clinical method due to its ease of coupling with traditional LC-MS methods and its promise for tuning separations to better resolve targeted and/or global isomers in complex biological samples.

Dataset Information

Effects of Detergent on ?-Synuclein Structure. A Native MS-Ion Mobility Study.

Publications

Effects of Detergent on α-Synuclein Structure. A Native MS-Ion Mobility Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets