ORCID Profile
0000-0003-2681-0370
Current Organisation
UNSW Sydney
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Publisher: Proceedings of the National Academy of Sciences
Date: 29-01-2018
Abstract: Metabolic dysfunction associated with decreased mitochondrial oxidative capacity is a major underlying cause of heart failure. Our study sheds new light on the potential role of bacteria-derived or endogenous siderophores as direct regulators of cardiomyocyte mitochondrial function. Furthermore, we demonstrate that lipocalin-2, a key feature of the innate immune response, facilitates the transport of siderophore–iron complexes into cells. This mechanism may have important physiological implications because elevated lipocalin-2 levels correlate positively with heart failure in humans, and mice lacking lipocalin-2 are protected from stress-induced mitochondrial dysfunction and heart failure.
Publisher: American Chemical Society (ACS)
Date: 15-10-2019
DOI: 10.1021/ACSCHEMBIO.9B00820
Abstract: Lcn2 is a host defense protein induced via the innate immune response to sequester iron-loaded bacterial siderophores. However, excess or prolonged elevation of Lcn2 levels can induce adverse cellular effects, including oxidative stress and inflammation. In this work, we use Hydrogen-Deuterium eXchange (HDX) and Isothermal Titration Calorimetry (ITC) to characterize the binding interaction between Lcn2 and siderophores enterobactin and 2,3-DHBA, in the presence and absence of iron. Our results indicate a rare "Type II" interaction in which binding of siderophores drives the protein conformational equilibrium toward an unfolded state. Linking our molecular model to cellular assays, we demonstrate that this "distorted binding mode" facilitates a deleterious cellular accumulation of reactive oxygen species that could represent the molecular origin of Lcn2 pathology. These results add important insights into mechanisms of Lcn2 action and have implications in Lcn2-mediated effects including inflammation.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.ACA.2022.339783
Abstract: Glycans are ubiquitous, structurally erse molecules that have specific and general roles involving metabolism, structure, and cell-to-cell signaling. Functional specificity depends strongly on the complexity of structures that polysaccharides can adopt based on their subunit composition, length, extent of branching, glycosidic bond connectivity and anomeric configuration. However, a rapid and comprehensive characterization of glycan isomers can be challenging owing to limitations associated with their separation. Here, ten composition, anomeric and connectivity disaccharide isomers were separated and detected using high-resolution differential ion mobility-mass spectrometry (DMS-MS, also known as FAIMS). Focus was primarily directed to compositional isomers corresponding to epimers that differ by the axial or equatorial position of a single hydroxyl group. DMS resolving power was enhanced 14-fold primarily by increasing the fraction of helium in the ion carrier gas and lowering the flow rate. At relatively high disaccharide concentrations, DMS-MS of each disaccharide resulted in complex and unique multi-peak spectra with up to ten fully and partially resolved peaks for β-1,4-mannobiose (Man-1,4β-Man), which can be attributed to the DMS separation and subsequent dissociation of ionic non-covalently bound oligomers into monomer ions. Each DMS spectrum has at least one differentiating peak that is not in the other spectra, indicating that DMS can be used to fully or partially resolve composition, configuration and connectivity isomers. At relatively low disaccharide concentrations, mixtures of disaccharide epimers can also be readily separated by DMS. The integration of high-resolution, ambient pressure DMS with complementary reduced-pressure ion mobility and MS-based glycomics and glycoproteomics workflows may be useful for improving the characterization of glycans and glycosylated biomolecules.
No related grants have been discovered for Xiaojing Huang.