A5026925202- Protein Structure and Dynamics
- Heat shock proteins research
- Enzyme Structure and Function
- Neuropeptides and Animal Physiology
- Computational Drug Discovery Methods
- Peptidase Inhibition and Analysis
- Mass Spectrometry Techniques and Applications
- Transgenic Plants and Applications
- Analytical Chemistry and Chromatography
- T-cell and B-cell Immunology
- Ion-surface interactions and analysis
- Autoimmune Neurological Disorders and Treatments
- Opioid Use Disorder Treatment
- Immunodeficiency and Autoimmune Disorders
- Neurotransmitter Receptor Influence on Behavior
- RNA and protein synthesis mechanisms
- Herpesvirus Infections and Treatments
- Tryptophan and brain disorders
- Diabetes Treatment and Management
- Pain Mechanisms and Treatments
- Metabolomics and Mass Spectrometry Studies
- Amino Acid Enzymes and Metabolism
- Substance Abuse Treatment and Outcomes
- Chemical Synthesis and Analysis
- Ocular Diseases and Behçet’s Syndrome
Technical University of Munich
2019-2023
Target (Germany)
2023
Helmholtz Zentrum München
2019-2022
Center for Integrated Protein Science Munich
2019-2022
Institute for Research in Biomedicine
2011-2016
Universitat de Barcelona
2011-2016
Hospital Universitari de Santa Maria
2016
Fundació Clínic per a la Recerca Biomèdica
2016
Barcelona Biomedical Research Park
2013
Weatherford College
2011
Abstract The heat shock protein 90 (Hsp90) is a molecular chaperone that employs the free energy of ATP hydrolysis to control folding and activation several client proteins in eukaryotic cell. To elucidate how local ATPase reaction active site couples global conformational dynamics Hsp90, we integrate here large-scale simulations with biophysical experiments. We show switching conserved ion pairs between N-terminal domain, harbouring site, middle domain strongly modulates catalytic barrier...
Abstract The co-chaperone p23 is a central part of the Hsp90 machinery. It stabilizes closed conformation Hsp90, inhibits its ATPase and important for client maturation. Yet, how this achieved has remained enigmatic. Here, we show that tryptophan residue in proximal region tail decelerates by allosterically switching catalytic loop Hsp90. We further NMR spectroscopy interacts with binding site via conserved helix. This helical motif also binds to protein glucocorticoid receptor (GR) free...
Hsp90 is a molecular chaperone that interacts with specific set of client proteins and assists their folding. The underlying mechanisms, involving dynamic transitions between open closed conformations, are still enigmatic. Combining nuclear magnetic resonance, small-angle x-ray scattering, biochemical experiments, we have identified key intermediate state induced by adenosine triphosphate (ATP) binding, in which rotation the N-terminal domain (NTD) yields arrangement poised for closing. This...
Abstract The molecular chaperone Hsp90 is an important regulator of proteostasis. It has remained unclear why S. cerevisiae possesses two isoforms, the constitutively expressed Hsc82 and stress-inducible Hsp82. Here, we report distinct differences despite a sequence identity 97%. Consistent with its function under stress conditions, Hsp82 more stable refolds efficiently than Hsc82. isoforms also differ in their ATPases conformational cycles. processive populates closed states to greater...
The molecular chaperone Hsp90 supports the functional activity of specific substrate proteins (clients). For client processing, dimer undergoes a series ATP-driven conformational rearrangements. Flexible linkers connecting three domains are crucial to enable dynamic arrangements. long charged linker N-terminal (NTD) and middle (MD) exhibits additional functions in vitro vivo. structural basis for these remains unclear. Here, we characterize conformation dynamics NTD-MD domain interactions by...
Abstract The functionality of most secreted proteins depends on their assembly into a defined quaternary structure. Despite this, it remains unclear how cells discriminate unassembled en route to the native state from misfolded ones that need be degraded. Here we show chaperones can regulate and control heterodimeric proteins, using interleukin 23 (IL-23) as model. We find IL-23 α-subunit partially unstructured until with its β-subunit occurs identify major site incomplete folding....
Deciphering conformational dynamics is crucial for understanding the biological functions of proteins and designing compounds targeting them. In particular, providing an accurate description microsecond-millisecond motions opens opportunity regulating protein-protein interactions (PPIs) by modulating one interacting partner. Here we analyzed prolyl oligopeptidase (POP) effects active-site-directed inhibitors on dynamics. We used integrated structural biology approach based NMR spectroscopy...
Ion mobility coupled to mass spectrometry (IMMS) is a technique that simultaneously separates gaseous ions on the basis of their mass, shape and size. The continuous advances in native applied IMMS have prompted its application structural study biomolecules. Hence, challenging systems terms molecular size, complexity heterogeneity can be transferred gas phase properties analyzed. Although low resolution technique, silico theoretical models or simulations provide valuable microscopic...
Ion mobility mass spectrometry (IMMS) is a biophysical technique that allows the separation of isobaric species on basis their size and shape. The high capacity, sensitivity relatively fast time scale measurements confer IMMS great potential for study proteins in slow (µs-ms) conformational equilibrium solution. However, use this examining dynamic still not generalized. One major limitations instability protein ions gas phase, which raises question as to what extent structures detected...
The heat shock protein 90 (Hsp90) is a molecular chaperone central to client folding and maturation in eukaryotic cells. During its cycle, Hsp90 undergoes ATPase-coupled large-scale conformational changes between open closed states, where the N-terminal middle domains of form compact dimerized conformation. However, principles switching motion states remain poorly understood. Here we show by integrating atomistic coarse-grained simulations with small-angle X-ray scattering experiments NMR...
Introduction Anti-NMDA encephalitis normally appears as a characteristic syndrome with typical symptoms that undergoes multiphase evolution. However, it sometimes develops atypical so we must perform careful differential diagnosis. Objectives To conduct current review of detection and management anti-NMDAr encephalitis, psychiatric manifestations. Method Systematic the literature in English (PubMed), following keywords: “Autoimmune encephalitis”, “psychosis”, “NMDA receptor”. Results We...
Introduction Every more often, there is evidence that shows a relationship between psychiatric symptoms and autoimmune disorders. Such the case of anti-NMDAR encephalitis, in which it has been recently described development psychotic symptoms. Anti-NMDAR encephalitis an disorder involves IgG autoantibodies against NMDA receptor subunit GluN1. This last fact could support with glutamatergic model schizophrenia. Objective To conduct current review to deepen detection management due frequent...
Abstract Review: 63 refs.