NSMB’s 30th anniversary

Over the past 30 years, Nature Structural & Molecular Biology (NSMB) has covered an enormous breadth of subjects in the broad field of molecular and structural biology. Here, some of the journal’s past and present editors recount their editorial experience at NSMB and some of the more memorable papers they worked on.

January 2024 marks 30 years since we published our first volume. Throughout the upcoming year, we will be celebrating this milestone, reflecting on the road covered and looking toward the future — with the help of our readers.

The first membrane protein structure was reported almost 40 years ago. In this issue, we are publishing a set of papers that serve to underline the incredible advances in our understanding of the biology of these multifaceted molecular machines.

In addition to the usual dose of compelling science, our March issue features thoughtful reflections on the last 30 years from readers, as well as past and present editors. Perhaps influenced by these pieces or by our stunning cover — or maybe it is just the changing seasons — we are in an introspective mood this month.

First discovered more than five decades ago, protein ubiquitylation has proven to be an omnipresent post-translational modification regulating virtually every eukaryotic cellular process. With novel clinical applications and recent studies demonstrating ubiquitylation of biomolecules other than proteins, the interest in ubiquitin will not waver any time soon.

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.

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?

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.

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.

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.

In this Perspective, the author describes the recent progress in understanding solute carrier (SLC) biology and discusses the roles of new families of atypical SLCs.

In this Review, the authors present an overview of our current understanding of the relationship between DNA methylation and three-dimensional chromatin architecture, discussing the extent to which DNA methylation may regulate the folding of the genome.

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.

Here, the authors discuss the various roles of the HUSH transcriptional silencing complex and its dysregulation in disease.