About this Research Topic
Now, as never before in the history of humankind, people are constantly communicating and aware of their surroundings. It is astonishing to see how similar our society is to a basic cellular organism, a society of cells. In order to function and survive, cells need to communicate with each other and gather information about the external environment. They do not use mobiles or social media, but they are able to codify and transfer information using signalling pathways.
Signalling pathways are characterised by networks of protein-protein and protein-nucleic acid interactions. Nearly all cellular processes are controlled by such interactions, including motility, growth, proliferation, gene expression, survival and apoptosis. Signalling pathways are stimulated by binding of extra- or intra-cellular signalling molecules to receptors, which relay such signals via binding to downstream targets. The flow of information through the cell is mediated by specific, selective interactions, which determine the route a pathway will follow and its functional outcome. As such, the formation of the correct protein complex in response to a specific signal is critical for cellular function. Proteins involved in cellular signalling can be enzymatically active and transfer information by altering stability, dynamics, structure, activity or cellular localisation of the targets. Many scaffolding proteins also contribute to the correct spatial and temporal formation of signalling complexes. The resulting processes are tightly regulated and their misregulation has been associated with complex human pathologies, including cancer and neurodegenerative disorders. The study of signalling networks offers therefore opportunities to identify and exploit therapeutic vulnerabilities in disease.
Structural biology, a field that has gained enormous momentum in the post-genomic era, has offered unprecedented insight into the function and regulation of protein-interaction networks. Advances at third generation synchrotron sources - including faster detectors, automation, brighter beam, improved software - have opened up opportunities for macromolecular crystallography, increasing speed of data collection from 4 crystals per hour to more than 20. The use of XFELs is having a massive impact on solving structure and dynamics of macromolecules from microcrystals. The technical advances in crystallography have also fuelled the so called "resolution revolution", transforming cryo-EM to the point where structure of medium-large macromolecules can be solved at atomic resolution. Cryo-EM has transformed the structural biology field and, in recognition for their work in developing this technique, Jacques Dubochet, Joachim Frank and Richard Henderson were awarded the Nobel Prize in Chemistry in 2017.
This Research Topic aims to capture the state of the art of this broad field, focusing on the study of protein complexes, which are components of signalling pathways, utilizing experimental or computational structural approaches. This work will provide an international platform for researchers to communicate the development of hybrid methods seeking to comprehensively understand cellular machines, their function and regulation.
Keywords: structural biology, protein complexes, signalling pathways, crystallography
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