Thomas Boesen

Thomas Boesen
Aarhus University | AU · Interdisciplinary Nanoscience Centre iNANO

PhD

About

99
Publications
10,533
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1,709
Citations
Citations since 2017
42 Research Items
1210 Citations
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20172018201920202021202220230100200300
20172018201920202021202220230100200300
20172018201920202021202220230100200300

Publications

Publications (99)
Article
Full-text available
The metzincin metalloproteinase PAPP-A plays a key role in the regulation of insulin-like growth factor (IGF) signaling by specific cleavage of inhibitory IGF binding proteins (IGFBPs). Using single-particle cryo-electron microscopy (cryo-EM), we here report the structure of PAPP-A in complex with its endogenous inhibitor, stanniocalcin-2 (STC2), n...
Preprint
Phosphorus is an essential macronutrient for all microorganisms and can be extracted from the environment by several metabolic pathways. In Escherichia coli, the 14-cistron phn operon encoding the carbon-phosphorus (C-P) lyase enzymatic machinery allows for extraction of phosphorus from a wide range of phosphonates characterised by the highly stabl...
Article
Full-text available
Microbially-produced ice nucleating proteins (INpro) are unique molecular structures with the highest known catalytic efficiency for ice formation. Airborne microorganisms utilize these proteins to enhance their survival by reducing their atmospheric residence times. INpro also have critical environmental effects including impacts on the atmospheri...
Article
Phosphorus (P) is an essential macronutrient that can be extracted from the environment by several metabolic pathways. In E. coli, phosphate deprivation activates the the 14-cistron phn operon that encodes carbon-phosphorus (C-P) lyase. C-P lyase confers the ability to extract phosphorus from a wide range of phosphonate compounds containing the che...
Article
Insulin regulates glucose homeostasis via binding and activation of the insulin receptor dimer at two distinct pairs of binding sites 1 and 2. Here, we present cryo-EM studies of full-length human insulin receptor (hIR) in an active state obtained at non-saturating, physiologically relevant insulin conditions. Insulin binds asymmetrically to the re...
Preprint
Microbially-produced ice nucleating proteins (INpro) are unique molecular structures with the highest known catalytic efficiency for ice formation. Their critical role in rain formation and frost damage of crops together with their diverse commercial applications warrant an in-depth understanding of their inherent ice nucleation mechanism. We used...
Preprint
Full-text available
Cotranscriptional folding of RNA is a fundamental self-assembly process of nature, important for the biological assembly of complex molecular machines like the ribosome. Inspired by this folding process, we developed the cotranscriptional RNA origami design method to efficiently produce RNA nanostructures by enzymatic synthesis, advantageous for la...
Article
Clostridioides difficile infections have emerged as the leading cause of healthcare-associated infectious diarrhea. Disease symptoms are mainly caused by the virulence factors, TcdA and TcdB, which are large homologous multidomain proteins. Here, we report a 2.8 Å resolution cryo-EM structure of native TcdA, unveiling its conformation at neutral pH...
Article
Extracellular electron transport in Geobacter has long been ascribed to conductive pili. Cryogenic electron microscopy now reveals non-conductive filaments made of pilin-heterodimer subunits. The combined data support a role for Geobacter pili in cytochrome-nanowire secretion instead of conduction.
Article
Full-text available
Transport of microbes in the atmosphere allows them to spread and to colonize new habitats. To survive the harsh environmental conditions encountered in the atmosphere, these microorganisms have to possess properties that allow them to resist atmospheric stress. We combined physiological experiments and genome analysis of Pseudomonas syringae strai...
Article
P4-ATPases define a eukaryotic subfamily of the P-type ATPases, and are responsible for the transverse flip of specific lipids from the extracellular or luminal leaflet to the cytosolic leaflet of cell membranes. The enzymatic cycle of P-type ATPases is divided into autophosphorylation and dephosphorylation half-reactions. Unlike most other P-type...
Article
Full-text available
Ice-nucleation active (INA) bacteria can promote the growth of ice more effectively than any other known material. Using specialized ice-nucleating proteins (INPs), they obtain nutrients from plants by inducing frost damage and, when airborne in the atmosphere, they drive ice nucleation within clouds, which may affect global precipitation patterns....
Preprint
Full-text available
The histidine-rich Ca ²⁺ -binding protein (HRC) stimulates the sarco-endoplasmic reticulum Ca ²⁺ -ATPase (SERCA) to increase Ca ²⁺ -uptake into the lumen. HRC also binds the triadin scaffold in a Ca ²⁺ -dependent manner, and HRC tunes both the uptake and release of Ca ²⁺ depending on the concentration in the intracellular Ca ²⁺ -stores. We investig...
Article
Nanoparticles can acquire a biomolecular corona with a species-specific biological identity. However, "non-self" incompatibility of recipient biological systems is often not considered, for example, when rodents are used as a model organism for preclinical studies of biomolecule-inspired nanomedicines. Using zebrafish embryos as an emerging model f...
Article
Ionotropic glutamate receptors are ligand‐gated ion channels governing neurotransmission in the central nervous system. Three major types of antagonists are known for the AMPA‐type receptor GluA2: competitive, non‐competitive (i.e. negative allosteric modulators; NAMs) used for treatment of epilepsy, and uncompetitive antagonists. We here report a...
Article
Polymer–lipid hybrid vesicles are an emerging type of nano‐assemblies that show potential as artificial organelles among others. Phospholipids and poly(cholesteryl methacrylate)‐block ‐poly(methionine methacryloyloxyethyl ester (METMA)—random– 2‐carboxyethyl acrylate (CEA)) labeled with a Förster resonance energy transfer (FRET) reporter pair are u...
Preprint
Full-text available
Ice-nucleation active (INA) bacteria can promote the growth of ice more effectively than any other known material. Utilizing specialized ice-nucleating proteins (INPros), they obtain nutrients from plants by inducing frost damage and, when airborne in the atmosphere, they drive ice nucleation within clouds and may affect global precipitation patter...
Article
Full-text available
Herein, we characterize the cellular uptake of a DNA structure generated by rolling circle DNA amplification. The structure, termed nanoflower, was fluorescently labeled by incorporation of ATTO488-dUTP allowing the intracellular localization to be followed. The nanoflower had a hydrodynamic diameter of approximately 300 nanometer and was non-toxic...
Preprint
Full-text available
A central paradigm in pattern recognition is self/non-self discrimination that remains largely unknown in the light of biological identities nanoparticles acquire in vivo and in vitro . Using zebrafish embryos as an in vivo model for real-time and ultrastructural imaging, here we unravelled the fate of intravenously injected SiO 2 nanoparticles wit...
Article
Full-text available
Bioelectricity generation, by Shewanella oneidensis (S. oneidensis) MR-1, has become particularly alluring, thanks to its extraordinary prospects for energy production, pollution treatment, and biosynthesis. Attempts to improve its technological output by modification of S. oneidensis MR-1 remains complicated, expensive and inefficient. Herein, we...
Article
Full-text available
Neurotransmitter:sodium symporters (NSS) are conserved from bacteria to man and serve as targets for drugs, including antidepressants and psychostimulants. Here we report the X-ray structure of the prokaryotic NSS member, LeuT, in a Na+/substrate-bound, inward-facing occluded conformation. To obtain this structure, we were guided by findings from s...
Article
Despite the common knowledge that the reticuloendothelial system is largely responsible for blood clearance of systemically administered nanoparticles, the sequestration mechanism remains a "black box". Using transgenic zebrafish embryos with cell type-specific fluorescent reporters and fluorescently-labelled model nanoparticles (70 nm SiO2), we he...
Article
Cable bacteria of the family Desulfobulbaceae form centimeter-long filaments comprising thousands of cells. They occur worldwide in the surface of aquatic sediments, where they connect sulfide oxidation with oxygen or nitrate reduction via long-distance electron transport. In the absence of pure cultures, we used single-filament genomics and metage...
Article
Full-text available
Type 4 P-type ATPases (P4-ATPases) are lipid flippases that drive the active transport of phospholipids from exoplasmic or luminal leaflets to cytosolic leaflets of eukaryotic membranes. The molecular architecture of P4-ATPases and the mechanism through which they recognize and transport lipids have remained unknown. Here we describe the cryo-elect...
Article
Full-text available
Model building into experimental maps is a key element of structural biology, but can be both time consuming and error prone for low-resolution maps. Here we present Namdinator, an easy-to-use tool that enables the user to run a molecular dynamics flexible fitting simulation followed by real-space refinement in an automated manner through a pipelin...
Article
Artificial organelles are envisioned as nanosized assemblies with intracellular biocatalytic activity to provide the host cells with non-native or missing/lost function. Hybrid vesicles loaded with glucose oxidase (NRGOx) or β-galactosidase (NRβ-Gal) and equipped with lysosomal escape ability are assembled using phospholipids and the block copolyme...
Preprint
Full-text available
P4-ATPases are lipid flippases that drive active transport of phospholipids from the exoplasmic or lumenal to the cytosolic leaflets of eukaryotic membranes to maintain their asymmetric lipid composition. The molecular architecture of P4-ATPases and how they work in lipid recognition and transport has remained elusive. Using cryo-electron microscop...
Article
Full-text available
The full length human histone 3 lysine 4 demethylase KDM5B (PLU-1/Jarid1B) has been studied using Hydrogen/Deuterium exchange mass spectrometry, homology modelling, sequence analysis, small angle X-ray scattering and electron microscopy. This first structure on an intact multi-domain Jumonji histone demethylase reveal that the so-called PLU region,...
Preprint
Full-text available
Model building into experimental maps is a key element of structural biology, but can be both time consuming and error-prone. Here we present Namdinator, an easy-to-use tool that enables the user to run a Molecular Dynamics Flexible Fitting (MDFF) simulation in an automated manner through a pipeline system. Namdinator will modify an atomic model to...
Article
Full-text available
Cable bacteria are long, multicellular micro-organisms that are capable of transporting electrons from cell to cell along the longitudinal axis of their centimeter-long filaments. The conductive structures that mediate this long-distance electron transport are thought to be located in the cell envelope. Therefore, this study examines in detail the...
Article
Airborne dispersal of microorganisms influences their biogeography, gene flow, atmospheric processes, human health and transmission of pathogens that affect humans, plants and animals. The extent of their impact depends essentially on cell-survival rates during the process of aerosolization. A central factor for cell-survival is water availability...
Article
Ice nucleation active bacteria have attracted particular attention due to their unique ability to produce specific ice nucleation proteins (INpros), which are the most efficient ice nuclei known as they induce nucleation at temperatures close to 0°C. Our model bacterium Pseudomonas syringae strain R10.79 produced INpros containing 67 tandem repeats...
Article
The human proton coupled folic acid transporter PCFT is the major import route for dietary folates. Mutations in the gene encoding PCFT cause hereditary folic acid malabsorption, which manifests itself by compromised folate absorption from the intestine and also in impaired folate transport in to the central nervous system. Since its recent discove...
Article
Full-text available
Type IV pili are important virulence factors on the surface of many pathogenic bacteria and have been implicated in a wide range of diverse functions including attachment, twitching motility, biofilm formation and horizontal gene transfer. The respiratory pathogen Streptococcus pneumoniae deploys type IV pili to take up DNA during transformation. T...
Article
Full-text available
This study investigates the impact of fatty acids on the cloud condensation nuclei (CCN) activity of sea salt aerosol of initial size 30, 50, 70 or 90 nm. Two of the major fatty acids in the marine environment, palmitic acid (C16) and stearic acid (C18), were investigated along with their unsaturated analogues palmitoleic acid and oleic acid, respe...
Article
The repressive Nucleosome Remodeling and histone Deacetylation (NuRD) complex remodels the chromatin structure by coupling ATP-dependent remodeling activity with histone deacetylase function and plays important roles in regulating gene transcription, DNA damage repair and chromatin assembly. The complex is composed of six subunits: Metastasis Assoc...
Article
Full-text available
Bacterial members of the neurotransmitter:sodium symporter (NSS) family perform Na⁺-dependent amino-acid uptake and extrude H⁺ in return. Previous NSS structures represent intermediates of Na⁺/substrate binding or intracellular release, but not the inward-to-outward return transition. Here we report crystal structures of Aquifex aeolicus LeuT in an...
Data
Supplementary Figures 1-5, Supplementary Table 1, Supplementary Discussion and Supplementary References
Data
The movie depicts the transition between two LeuT return states in pH 6.5 structure Molecule A and B, zoomed in at the extracellular side. The movie was prepared by 'morphing' from Molecule A to Molecule B and back. TM1b (red cartoon) fluctuates to some extent at the extracellular side, however Leu25 (red sticks) is stable at its position. The majo...
Data
The movie depicts the full transport cycle of the NSS family going from the outward-facing return state (presented here) through all known states of the NSS cycle (see supplementary discussion and supplementary figure 6 for further details). The movie 'morphs' between available structures - LeuT outward-facing, Na+-free return state (this study), L...
Chapter
Nanodiscs are disc-shaped self-assembled lipid bilayers encircled by membrane scaffolding proteins derived from Apolipoprotein A-1 (apo A-1). They constitute a versatile tool for studying membrane proteins since reconstitution into nanodiscs allows studies of the membrane proteins in detergent-free aqueous solutions in a lipid bilayer. Here, we app...
Article
Full-text available
Membrane proteins are key players in biological systems, mediating signalling events and the specific transport of e.g. ions and metabolites. Consequently, membrane proteins are targeted by a large number of currently approved drugs. Understanding their functions and molecular mechanisms is greatly dependent on structural information, not least on...
Article
Full-text available
Exploiting the anomalous signal of the intrinsic S atoms to phase a protein structure is advantageous, as ideally only a single well diffracting native crystal is required. However, sulfur is a weak anomalous scatterer at the typical wavelengths used for X-ray diffraction experiments, and therefore sulfur SAD data sets need to be recorded with a hi...
Article
Full-text available
Type IV pili are widely expressed among Gram-negative bacteria, where they are involved in biofilm formation, serve in the transfer of DNA, motility and in the bacterial attachment to various surfaces. Type IV pili in Shewanella oneidensis are also supposed to play an important role in extracellular electron transfer by the attachment to sediments...
Article
Full-text available
Unlabelled: The members of the oligoadenylate synthetase (OAS) family of proteins are antiviral restriction factors that target a wide range of RNA and DNA viruses. They function as intracellular double-stranded RNA (dsRNA) sensors that, upon binding to dsRNA, undergo a conformational change and are activated to synthesize 2'-5'-linked oligoadenyl...
Presentation
Full-text available
The advantage of using the anomalous signal of sulfur for phase determination is that only a single, well-diffracting crystal is needed and that a native structure will be obtained. Using long-wavelength S-SAD to a resolution of 1.9 Å we have determined the novel structure of an 89 residue protein with only 2 Cysteines fixed in a disulfide bridge....
Article
Full-text available
The THO complex participates during eukaryotic mRNA biogenesis in coupling transcription to formation and nuclear export of translation-competent messenger ribonucleoprotein particles. In Saccharomyces cerevisiae, THO has been defined as a heteropentamer composed of the Tho2p, Hpr1p, Tex1p, Mft1p, and Thp2p subunits and the overall three-dimensiona...
Article
Full-text available
ABSTRACT The discovery of bacterial conductive structures, termed nanowires, has intrigued scientists for almost a decade. Nanowires enable bacteria to transfer electrons over micrometer distances to extracellular electron acceptors such as insoluble metal oxides or electrodes. Nanowires are pilus based and in Geobacter sulfurreducens are composed...
Article
Aggregatibacter actinomycetemcomitans is a gram-negative, facultatively anaerobic cocco-bacillus and a frequent member of the human oral flora. It produces a leukotoxin, LtxA, belonging to the repeats-in-toxin (RTX) family of bacterial cytotoxins. LtxA efficiently kills neutrophils and mononuclear phagocytes. The known receptor for LtxA on leukocyt...
Article
The complement system constitutes an important barrier to infection of the human body. Over more than four decades structural properties of the proteins of the complement system have been investigated with X-ray crystallography, electron microscopy, small-angle scattering, and atomic force microscopy. Here, we review the accumulated evidence that t...
Article
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CD18 integrins are adhesion molecules expressed on the cell surface of leukocytes and play a central role in the molecular mechanisms supporting leukocyte migration to zones of inflammation. Recently, it was discovered that CD11a/CD18 is shed from the leukocyte surface in models of inflammation. In this study, we show that shedding of human CD11/CD...
Article
Full-text available
The binding of Abs to microbial surfaces followed by complement activation constitutes an important line of defense against infections. In this study, we have investigated the relationship between complement activation and the binding of human IgM Abs to surfaces with different curvatures. IgM Abs to dextran were shown to activate complement potent...
Article
Full-text available
Vacuolar H+‐ATPases (V‐ATPases) were discovered more than 30 years ago. They are related to the F‐ATPases—that is, ATP synthases—but have been refined for proton pumping by the rotary ATPase activity and are responsible for the acidification of intracellular compartments. Acidification is crucial for the function of many organelles and vesicles in...
Article
Full-text available
Elongation factor eEF3 is an ATPase that, in addition to the two canonical factors eEF1A and eEF2, serves an essential function in the translation cycle of fungi. eEF3 is required for the binding of the aminoacyl-tRNA–eEF1A–GTP ternary complex to the ribosomal A-site and has been suggested to facilitate the clearance of deacyl-tRNA from the E-site....