A5050842384- Ubiquitin and proteasome pathways
- 14-3-3 protein interactions
- interferon and immune responses
- Toxin Mechanisms and Immunotoxins
- PI3K/AKT/mTOR signaling in cancer
- Cellular transport and secretion
- Biochemical and Structural Characterization
- Enzyme Structure and Function
- Field-Flow Fractionation Techniques
- Protein Degradation and Inhibitors
- thermodynamics and calorimetric analyses
- Neurobiology and Insect Physiology Research
- Bacterial Genetics and Biotechnology
- Spaceflight effects on biology
- ATP Synthase and ATPases Research
- Immune Response and Inflammation
- Tardigrade Biology and Ecology
- HIV Research and Treatment
- Nanoplatforms for cancer theranostics
- Fungal and yeast genetics research
- vaccines and immunoinformatics approaches
- RNA and protein synthesis mechanisms
- Inflammasome and immune disorders
- Photosynthetic Processes and Mechanisms
- Calcium signaling and nucleotide metabolism
MRC Laboratory of Molecular Biology
2010-2023
Medical Research Council
2010-2021
Antibodies provide effective antiviral immunity despite the fact that viruses escape into cells when they infect. Here we show antibodies remain attached to after cell infection and mediate an intracellular immune response disables virions in cytosol. We have discovered possess a cytosolic IgG receptor, tripartite motif-containing 21 (TRIM21), which binds with higher affinity than any other receptor human body. TRIM21 rapidly recruits incoming antibody-bound virus targets it proteasome via...
Opening up Vps34 protein complexes During intracellular membrane trafficking, large regulate and adapt the activity of signal transducer enzymes such as class III phosphatidylinositol 3-kinase Vps34. These enzyme are present in all eukaryotic cells, having widespread importance neurodegeneration, aging, cancer; however, a structural understanding has been lacking. Rostislavleva et al. provide atomic-resolution insights into structures Vps34-containing required for autophagy, endocytic...
Mastering regulation The mechanistic target of rapamycin complex 1 (mTORC1) is known as the master kinase, acknowledging its key role in integrating multiple signals to regulate cell growth. When nutrients are abundant, heterodimers Rag, a class small guanosine triphosphatase, bind mTORC1 and recruit it lysosome. Here, other signaling pathways converge on complex. Anandapadamanaban et al. determined cryo–electron microscopy crystal structures RagA/RagC heterodimer. structures, together with...
Fast synaptic neurotransmission in the vertebrate central nervous system relies primarily on ionotropic glutamate receptors (iGluRs), which drive neuronal excitation, and type A γ-aminobutyric acid (GABA Rs), are responsible for inhibition. However, GluD1 receptor, an iGluR family member, is present at both excitatory inhibitory synapses. Whether how activation may affect unknown. In this work, by using a combination of biochemical, structural, functional analyses, we demonstrate that binds...
Abstract Web spiders connect silk proteins, so-called spidroins, into fibers of extraordinary toughness. The spidroin N-terminal domain (NTD) plays a pivotal role in this process: it polymerizes spidroins through complex mechanism dimerization. Here we analyze sequences NTDs and find an unusually high content the amino acid methionine. We simultaneously mutate all methionines present hydrophobic core NTD from nursery web spider’s dragline to leucine. mutated is strongly stabilized folds at...
Microscale thermophoresis (MST), and the closely related Temperature Related Intensity Change (TRIC), are synonyms for a recently developed measurement technique in field of biophysics to quantify biomolecular interactions, using (capillary-based) NanoTemper Monolith (multiwell plate-based) Dianthus instruments. Although this has been extensively used within scientific community due its low sample consumption, ease use, ubiquitous applicability, MST/TRIC not enjoyed unambiguous acceptance...
A number of intrinsically disordered proteins (IDPs) encoded in stress-tolerant organisms, such as tardigrade, can confer fitness advantage and abiotic stress tolerance when heterologously expressed. Tardigrade-specific including the cytosolic-abundant heat-soluble are proposed to through vitrification or gelation, whereas evolutionarily conserved IDPs tardigrades may contribute other biophysical mechanisms. In this study, we characterized mechanism action an conserved, tardigrade IDP,...
SUMMARY Trim-Away is a powerful new technology that exploits off-the-shelf antibodies and the E3 RING ligase cytosolic antibody receptor TRIM21 to carry out rapid protein depletion. How catalytically-activated upon substrate engagement during either its normal immune function or when re-purposed for targeted degradation unknown. Here we show mechanism of substrate-induced clustering triggers intermolecular dimerization domain switch on ubiquitination activity induce an antiviral response...
The tripartite motif (TRIM) proteins are a large family of >100 members, several which have important roles in antiviral immunity and innate immune signaling. TRIM5α associates with incoming HIV-1 capsids, interfering controlled disassembly targeting them for degradation by the proteasome. TRIM21 is cytosolic antibody receptor, also targets viral capsids proteasomal degradation. TRIM25 involved immunity, being essential ubiquitination RIG-I. Recent positive selection analysis has...
Abstract Eukaryotic cells coordinate growth with the availability of nutrients through protein kinase complex mTORC1, which is part a pathway that often upregulated in cancer. The mTORC1 activated by association two types GTPases, Rags and RHEB. heterodimeric Rag GTPases are key components activation response to amino acids. heterodimer interacts RAPTOR subunit manner dependent on nucleotide-bound states its constituent GTPases. We used hydrogen/deuterium exchange mass spectrometry (HDX-MS)...