Schumacher, S., Dedden, D., Nunez, R.V., Matoba, K., Takagi, J., Biertümpfel, C., and Mizuno, N.
Science advances, 2021, 7.
Structural insights into integrin α 5 β 1 opening by fibronectin ligand
Integrin α5β1 is a major fibronectin receptor critical for cell migration. Upon complex formation, fibronectin and α5β1 undergo conformational changes. While this is key for cell-tissue connections, its mechanism is unknown. Here, we report cryo-electron microscopy structures of native human α5β1 with fibronectin to 3.1-angstrom resolution, and in its resting state to 4.6-angstrom resolution. The α5β1-fibronectin complex revealed simultaneous interactions at the arginine-glycine-aspartate loop, the synergy site, and a newly identified binding site proximal to adjacent to metal ion-dependent adhesion site, inducing the translocation of helix α1 to secure integrin opening. Resting α5β1 adopts an incompletely bent conformation, challenging the model of integrin sharp bending inhibiting ligand binding. Our biochemical and structural analyses showed that affinity of α5β1 for fibronectin is increased with manganese ions (Mn2+) while adopting the half-bent conformation, indicating that ligand-binding affinity does not depend on conformation, and α5β1 opening is induced by ligand-binding.
What exactly happens when the coronavirus SARS-CoV-2 infects a cell? In an article published in Nature, a team from the Max Planck Institute of Biochemistry and the Technical University of Munich (TUM) paints a comprehensive picture of the viral infection process. For the first time, the interaction between the coronavirus and a cell is documented at five different proteomics levels during viral infection. This knowledge will help to gain a better understanding of the virus and find potential starting points for therapies.
When a virus enters a cell, viral and cellular protein molecules begin to interact. Both the replication of the virus and the reaction of the cells are the result of complex protein signaling cascades. A team led by Andreas Pichlmair, Professor of Immunopathology of Viral Infections at the Institute of Virology at TUM, and Matthias Mann, Head of the Department of Proteomics and Signal Transduction at the Max Planck Institute of Biochemistry, has systematically recorded how human lung cells react to individual proteins of the covid-19 pathogen SARS-CoV-2 and the SARS coronavirus, the latter of which has been known for some time.
Categorization is the brain’s tool to organize nearly everything we encounter in our daily lives. Grouping information into categories simplifies our complex world and helps us to react quickly and effectively to new experiences. Scientists at the Max Planck Institute of Neurobiology have now shown that also mice categorize surprisingly well. The researchers identified neurons encoding learned categories and thereby demonstrated how abstract information is represented at the neuronal level.
A toddler is looking at a new picture book. Suddenly it points to an illustration and shouts 'chair'. The kid made the right call, but that does not seem particularly noteworthy to us. We recognize all kinds of chairs as 'chair' without any difficulty. For a toddler, however, this is an enormous learning process. It must associate the chair pictured in the book with the chairs it already knows – even though they may have different shapes or colors. How does the child do that?
Müller-Reif, J.B., Hansen, F.M., Schweizer, L., Treit, P.V., Geyer, P.E., and Mann, M.
(IMPRS-LS students/alumni are in bold)
Mol Cell Proteomics, 2021, 100082, online ahead of print.
A new parallel high-pressure packing system enables rapid multiplexed production of capillary columns
Reversed-phase high performance liquid chromatography (HPLC) is the most commonly applied peptide separation technique in mass spectrometry-based proteomics. Particle-packed capillary columns are predominantly used in nano-flow HPLC systems. Despite being the broadly applied standard for many years capillary columns are still expensive and suffer from short lifetimes, particularly in combination with ultra-high-pressure chromatography systems. For this reason, and to achieve maximum performance, many laboratories produce their own in-house packed columns. This typically requires a considerable amount of time and trained personnel. Here, we present a new packing system for capillary columns enabling rapid, multiplexed column packing with pressures reaching up to 3000 bar. Requiring only a conventional gas pressure supply and methanol as driving fluid, our system replaces the traditional setup of helium pressured packing bombs. By using 10x multiplexing, we have reduced the production time to just under 2 minutes for several 50 cm columns with 1.9 um particle size, speeding up the process of column production 40 to 800 times. We compare capillary columns with various inner diameters (ID) and length packed under different pressure conditions with our newly designed, broadly accessible high-pressure packing station.
Biophysicists have shown that a phenomenon known as diffusiophoresis, which can lead to a directed particle transport, can occur in biological systems.
In order to perform their biological functions, cells must ensure that their logistical schedules are implemented smoothly, such that the necessary molecular cargoes are delivered to their intended destinations on time. Most of the known transport mechanisms in cells are based on specific interactions between the cargo to be transported and the energy-consuming motor proteins that convey the load to its destination. A group of researchers led by Petra Schwille of the Max Planck Institute for Biochemistry and LMU physicist Erwin Frey, Chair of Statistical and Biological Physics, has now shown for the first time that a form of directed transport of particles can take place in cells, even in the absence of molecular motors. Furthermore, this mechanism can sort the transported particles according to their size, as the team reports in the latest issue of Nature Physics.
Henneberg, L.T., and Schulman, B.A.
Cell Chem Biol, 2021, online ahead of print.
Decoding the messaging of the ubiquitin system using chemical and protein probes. Cell chemical biology
Post-translational modification of proteins by ubiquitin is required for nearly all aspects of eukaryotic cell function. The numerous targets of ubiquitylation, and variety of ubiquitin modifications, are often likened to a code, where the ultimate messages are diverse responses to target ubiquitylation. E1, E2, and E3 multiprotein enzymatic assemblies modify specific targets and thus function as messengers. Recent advances in chemical and protein tools have revolutionized our ability to explore the ubiquitin system, through enabling new high-throughput screening methods, matching ubiquitylation enzymes with their cellular targets, revealing intricate allosteric mechanisms regulating ubiquitylating enzymes, facilitating structural revelation of transient assemblies determined by multivalent interactions, and providing new paradigms for inhibiting and redirecting ubiquitylation in vivo as new therapeutics. Here we discuss the development of methods that control, disrupt, and extract the flow of information across the ubiquitin system and have enabled elucidation of the underlying molecular and cellular biology.