Biology subjects

Haupt, C.

Publications and source records attributed to Haupt, C..

6 recordsLinked to original sources

bioRxiv2026

An aged human bone marrow mesenchymal niche causes impaired function of human hematopoietic stem cells under regeneration-induced stress

Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) and are responsible for blood formation throughout life. With advancing age, HSCs show reduced functional capacity. While clear intrinsic cellular changes in human HSCs (hHSCs) occur during aging, it remains unclear how the human bone marrow (hBM) niche contributes to hHSC dysfunction. This research gap is largely due to a lack of suitable experimental models capable of replicating the organization and function of the aged hBM environment. This study demonstrates that aged hBM mesenchymal stromal cells (hBMSCs) act as important niche regulators of hHSC function by contributing to the myeloid-biased differentiation of young hHSCs. Furthermore, hBMSCs play a crucial role in protecting hHSCs during regeneration-induced stress while this protective function of hBMSCs is impaired with age.

cell biology↗

bioRxiv2026

Structural basis of Arf1-driven membrane tubulation

Membrane tubules form at Golgi compartments to facilitate membrane and cargo flow in intracellular trafficking. Here we show that the small GTPase Arf1, an inducer of membrane curvature and key regulator of trafficking, is able to form strongly curved tubules in the presence of lipids and GTP{gamma}S in vitro without the need for further coat components. Using cryo-electron microscopy, we determined the structures of tubular Arf1-scaffolds with diameters of 195 and 215 [A] at 3.1 and 3.8 [A] resolutions, respectively. The nucleotide-bound globular domains of Arf1 form polar helical lattices (i.e. directional assemblies with distinct start/finish orientations), with conserved interfaces and a consistent back-to-face orientation along the filaments. The rigid coat is tethered to the membrane by a flexible linker and anchored by an amphipathic helix (AH) that is free to diffuse and make space within the leaflet, allowing for accommodation of transmembrane cargo. The diversity of tubular diameters observed would allow various cargo sizes to be accommodated in the lumen, while maintaining the local coat architecture. Apart from serving as tubular transport intermediates, Arf1-scaffolds may also play a role at the neck of COPI vesicle on the route to scission.

biophysics↗

bioRxiv2021

Angicin, a novel bacteriocin of Streptococcus anginosus

As a conserved defense mechanism, many bacteria produce antimicrobial peptides, called bacteriocins, which give a colonization advantage in a multispecies environment. Here the first bacteriocin of Streptococcus anginosus, designated Angicin, is described. S. anginosus is commonly described as a commensal, however it also possesses a high pathogenic potential. Therefore, understanding factors contributing to its host colonization and persistence are important. A radial diffusion assay was used to identify S. anginosus BSU 1211 as a potent bacteriocin producer. By genetic mutagenesis the background of bacteriocin production and the bacteriocin gene itself were identified. Synthetic Angicin shows high activity against closely related streptococci, listeria and vancomycin resistant enterococci. It has a fast mechanism of action and causes a membrane disruption in target cells. Angicin, present in cell free supernatant, is insensitive to changes in temperature from -70 to 90 {degrees}C and pH values from 2-10, suggesting that it represents an interesting compound for potential applications in food preservation or clinical settings.

microbiology↗

bioRxiv2021

Protease Resistance of ex vivo Amyloid Fibrils implies the proteolytic Selection of disease-associated Fibril Morphologies

Several studies recently showed that ex vivo fibrils from patient or animal tissue were structurally different from in vitro formed fibrils from the same polypeptide chain. Analysis of serum amyloid A (SAA) and A{beta}-derived amyloid fibrils additionally revealed that ex vivo fibrils were more protease stable than in vitro fibrils. These observations gave rise to the proteolytic selection hypothesis that suggested that disease-associated amyloid fibrils were selected inside the body by their ability to resist endogenous clearance mechanisms. We here show, for more than twenty different fibril samples, that ex vivo fibrils are more protease stable than in vitro fibrils. These data support the idea of a proteolytic selection of pathogenic amyloid fibril morphologies and help to explain why only few amino acid sequences lead to amyloid diseases, although many, if not all, polypeptide chains can form amyloid fibrils in vitro.

biochemistry↗

bioRxiv2020

Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis

Systemic AL amyloidosis is a debilitating and potentially fatal disease that arises from the misfolding and fibrillation of immunoglobulin light chains (LCs). The disease is patient-specific with essentially each patient possessing a unique LC sequence. In this study, we present the first ex vivo fibril structures of a {lambda}3 LC. The fibrils were extracted from the explanted heart of a patient (FOR005) and consist of 115 residues, mainly from the LC variable domain. The fibril structures imply that a 180{degrees} rotation around the disulfide bond and a major unfolding step are necessary for fibrils to form. The two fibril structures show highly similar fibril protein folds, differing in only a 12-residue segment. Remarkably, the two structures do not represent separate fibril morphologies, as they can co-exist at different z-axial positions within the same fibril. Our data imply the presence of structural breaks at the interface of the two structural forms.

molecular biology↗

bioRxiv2018

Cross-linking/Mass Spectrometry: A Community-Wide, Comparative Study Towards Establishing Best Practice Guidelines

The number of publications in the field of chemical cross-linking combined with mass spectrometry (XL-MS) to derive constraints for protein three-dimensional structure modeling and to probe protein-protein interactions has largely increased during the last years. As the technique is now becoming routine for in vitro and in vivo applications in proteomics and structural biology there is a pressing need to define protocols as well as data analysis and reporting formats that are generally accepted in the field and that have shown to lead to high-quality results. This first, community-based harmonization study on XL-MS is based on the results of 32 groups participating worldwide. The aim of this paper is to summarize the status quo of XL-MS and to compare and evaluate existing cross-linking strategies. From the results obtained, common protocols will be established. Our study serves as basis for establishing best practice guidelines in the field for conducting cross-linking experiments, performing data analysis, and reporting formats with the ultimate goal of assisting scientists to generate accurate and reproducible XL-MS results.

biochemistry↗