Raphael Trenker
A5003054273- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- SARS-CoV-2 and COVID-19 Research
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Receptor Mechanisms and Signaling
- Computational Drug Discovery Methods
- Lipid Membrane Structure and Behavior
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Chemical Synthesis and Analysis
- RNA and protein synthesis mechanisms
- Advanced Biosensing Techniques and Applications
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Force Microscopy Techniques and Applications
- Molecular Communication and Nanonetworks
- Nanowire Synthesis and Applications
- SARS-CoV-2 detection and testing
- Advanced Electron Microscopy Techniques and Applications
- interferon and immune responses
- Mitochondrial Function and Pathology
- Metalloenzymes and iron-sulfur proteins
University of California, San Francisco
2019-2024
Goethe University Frankfurt
2024
Quantitative BioSciences
2020-2024
Walter and Eliza Hall Institute of Medical Research
2015-2023
Weizmann Institute of Science
2023
The University of Melbourne
2015-2022
Molecular Biology Consortium
2020-2021
University of Oxford
2017
Max Planck Institute of Biophysics
2015
A newly described coronavirus named severe acute respiratory syndrome 2 (SARS-CoV-2), which is the causative agent of disease 2019 (COVID-19), has infected over 2.3 million people, led to death more than 160,000 individuals and caused worldwide social economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for treatment COVID-19, nor there any vaccines that prevent infection SARS-CoV-2, efforts develop hampered by limited knowledge molecular details how SARS-CoV-2...
ABSTRACT An outbreak of the novel coronavirus SARS-CoV-2, causative agent COVID-19 respiratory disease, has infected over 290,000 people since end 2019, killed 12,000, and caused worldwide social economic disruption 1,2 . There are currently no antiviral drugs with proven efficacy nor there vaccines for its prevention. Unfortunately, scientific community little knowledge molecular details SARS-CoV-2 infection. To illuminate this, we cloned, tagged expressed 26 29 viral proteins in human...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the cell receptor angiotensin-converting enzyme (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt ACE2. Cryo-electron microscopy (cryo-EM) revealed one nanobody, Nb6, binds in fully inactive conformation with binding domains locked into their inaccessible down state, incapable...
Abstract The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis those remain unknown. Here, we report an atomic model for full-length obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. resulting reveals highly-conserved zinc ion-binding site, suggesting role RNA binding. Mapping emerging mutations variants on shows potential host-Nsp2 interaction regions....
De novo-designed receptor transmembrane domains (TMDs) present opportunities for precise control of cellular functions. We developed a de novo design strategy generating programmed membrane proteins (proMPs): single-pass α-helical TMDs that self-assemble through computationally defined and crystallographically validated interfaces. used these proMPs to program specific oligomeric interactions into chimeric antigen (CAR) we expressed in mouse primary T cells found both vitro CAR cell cytokine...
ABSTRACT Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. gains entry into host cells via interaction between its Spike protein the cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this confers potent neutralization viral entry, providing avenue for vaccine design therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt ACE2. By screening...
The mechanisms of assembly and function for many important type I/II (single-pass) transmembrane (TM) receptors are proposed to involve the formation and/or alteration specific interfaces among their membrane-embedded α-helical TM domains. application lipidic cubic phase (LCP) bilayer media crystallization single-α-helical complexes has potential provide valuable structural mechanistic insights into such systems. However, fidelity observed in crowded crystalline arrays been difficult...
Abstract PGAM5 is a mitochondrial protein phosphatase whose genetic ablation in mice results mitochondria-related disorders, including neurodegeneration. Functions of include regulation mitophagy, cell death, metabolism and aging. However, mechanisms regulating activation signaling are poorly understood. Using electron cryo-microscopy, we show that forms dodecamers solution. We also present crystal structure reveals the determinants dodecamer formation. Furthermore, observe assembly into...
Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) and Knob-associated Histidine-rich (KAHRP) are directly linked to malaria pathology. PfEMP1 KAHRP cluster on protrusions (knobs) the P. falciparum-infected erythrocyte surface enable pathogenic cytoadherence of infected erythrocytes host microvasculature, leading restricted blood flow, oxygen deprivation damage tissues. Here we characterize interactions with spectrin using biophysical, structural computational approaches. These...
A serial millisecond crystallography (SMX) facility has recently been implemented at the macromolecular beamline, MX2 Australian Synchrotron. The setup utilizes a combination of an EIGER X 16M detector system and in-house developed high-viscosity injector, “Lipidico.” Lipidico uses syringe needle to extrude microcrystal-containing viscous media it is compatible with commercially available syringes. sample delivery via protein crystals suspended in mixture frame rate enables high-throughput...
The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis those remain unknown. Here, we report an atomic model for full-length obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. resulting reveals highly-conserved zinc ion-binding site, suggesting role RNA binding. Mapping emerging mutations variants on shows potential host-Nsp2 interaction regions. Using...
Human Epidermal growth factor Receptor 4 (HER4 or ERBB4) carries out essential functions in the development and maintenance of cardiovascular nervous systems. HER4 activation is regulated by a diverse group extracellular ligands including neuregulin (NRG) family betacellulin (BTC), which promote homodimerization heterodimerization with other HER receptors. Important are exerted via its close homolog orphan receptor, HER2. To date structural insights into ligand-mediated have been limited to...
Obtaining well-diffracting crystals of membrane proteins, which is crucial to the molecular-level understanding their intrinsic three-dimensional structure, dynamics, and function, represents a fundamental bottleneck in field structural biology. One major advances protein determination was realization that nanostructured lipidic cubic phase (LCP) environment constitutes mimetic matrix promotes solubilization, stabilization, crystallization specific proteins. Despite two decades passing since...
For evolving biological and biomedical applications of hybrid protein?lipid materials, understanding the behavior protein within lipid mesophase is crucial. After more than two decades since invention in meso crystallization method, a protein-eye view its mechanism still lacking. Numerous structural studies have suggested that integral membrane proteins preferentially partition at localized flat points on bilayer surface cubic phase with crystal growth occurring from local fluid lamellar L?...
Immune-stimulatory ligands, such as major histocompatibility complex molecules and the T-cell costimulatory ligand CD86, are central to productive immunity. Endogenous mammalian membrane-associated RING-CHs (MARCH) act on these other targets regulate antigen presentation activation of adaptive immunity, whereas virus-encoded homologs target same evade immune responses. Substrate specificity is encoded in or near membrane-embedded domains MARCHs proteins they regulate, but exact sequences...
Cell-free systems exploit the transcription and translation machinery of cells from different origins to produce proteins in a defined chemical environment. Due its open nature, cell-free protein production is versatile tool introduce specific labels such as heavy isotopes, non-natural amino acids tags into while avoiding cell toxicity. In particular, radiolabelled peptides are valuable tools for functional characterization protein-protein interactions studying binding kinetics. this study...
Abstract De novo designed receptor transmembrane domains (TMDs) present opportunities for precise control of cellular functions. We developed a de design strategy generating programmed membrane proteins (proMPs): single-pass α-helical TMDs that self-assemble through computationally defined and crystallographically validated interfaces. used these proMPs to program specific oligomeric interactions into chimeric antigen (CAR) found both in vitro CAR T cell cytokine release vivo antitumor...