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Since Nature Structural and Molecular Biology was started 30 years ago, our understanding of transcription and mRNA processing has been revolutionized through structural and mechanistic studies. Here, we present our personal views of the advances in understanding the production of mature eukaryotic mRNAs over the past decade.
G protein-coupled receptors (GPCRs) with no known endogenous ligand are termed orphans. Deorphanization of a GPCR involves identifying the ligand, which can be a painstaking exercise. In this Comment, we discuss the challenges in the process, its role in drug discovery and alternative approaches to characterizing orphan GPCRs.
The identification of sodium and potassium currents as underlying action potential propagation, more than 70 years ago, opened a new avenue of research into the role of ion channels. In this Comment, we present our personal perspectives of the field, from the identification of Shaker as a potential potassium channel to the mechanistic insights available to us today.
Over the past 30 years, the field of structural biology and its associated biological insights have seen amazing progress. In this Comment, I recount several milestones in the field and how we can apply lessons from the past toward an exciting future, especially as it relates to drug discovery.
In addition to its role in proteasomal degradation, ubiquitin has multiple roles in autophagy. It can mark proteins for autophagic degradation and actively drive autophagosome formation. Recent work shows that ubiquitin can also be conjugated to phospholipids and other biomolecules.
Ubiquitination is an essential process that curtails cellular levels of damaged and redundant proteins. Chemical biologists have harnessed this natural system to induce the degradation of disease-relevant proteins. We reflect here on the potential of ‘degraders’ for targeted selectivity, and discuss the role of computer-aided drug design in shaping future advances.
The modification of proteins with the small protein ubiquitin constitutes a Daedalian system of posttranslational modifications in every eukaryotic cell, which is often referred to as the ubiquitin code1. Here we consider the scale and complexity of the ubiquitin system in light of recent developments.
Collaboration is key to modern science, with major advances using multiple complementary approaches and dependent on sophisticated infrastructure. Yet science is also highly personal, as each person carves out a reputation and career. How does this work out in reality, and how can communities be built to benefit science and scientists?
Here we investigate the role of epigenetics in the formation, transcription regulation, maintenance and termination of several non-canonical chromatin structures. Using two examples, we demonstrate how studying non-canonical structures may reveal underlying mechanisms with implications for disease and propose intriguing epigenetic avenues for further exploration.
The concluding statement of Watson and Crick’s historic paper on the structure of DNA1 enshrines a key tenet of molecular mechanistic cell biology: “… the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material”. Function — heredity in this case — is embedded in the redundant sequence information of the two strands of DNA. Although not always expressed as blatantly, the intimate dependence of cellular function on the mechanical level of macromolecules is inspirational. The devil is in the structural detail, and the painstaking quest for the correct details and their returns in the form of reliable knowledge knows no shortcuts.
