The ability to view structures of proteins at atomic resolution, facilitated by the rise of macromolecular crystallography, has had a tremendous impact in many areas of sciences, including molecular pharmacology, drug discovery and biotechnology. However, the teaching of macromolecular crystallography in universities across the globe has been less than optimal. This could be attributed to the interdisciplinary nature of this subject, making it appear esoteric and incomprehensible, at least at first glance, for students who have exclusive training in only one specific discipline. For the instructor, this problem is compounded further by the plethora of complex concepts and specialized terminologies that the science of macromolecular crystallography has accumulated over the course of its evolution. Moreover, the advent of robotics and several sophisticated software algorithms have reduced the incentive to understand the beautiful conceptual bedrock on which this subject is based. As a way of addressing some of the challenges delineated above, this Words of Advice article attempts to formulate the broad framework within which the teaching and learning of macromolecular crystallography should be approached. It advocates the acknowledgement that this is an interdisciplinary field, with substantial contributions from chemical, physical, biological and mathematical sciences, requiring the evolution of teaching approaches that acknowledge this reality. Moreover, it suggests the use of visual tools, use of computational resources and history to make the subject more relatable to students.

Phosphatidic acid (PA), the simplest phospholipid, acts as a key metabolic intermediate and second messenger that impacts diverse cellular and physiological processes across species ranging from microbes to plants and mammals. The cellular levels of PA dynamically change in response to stimuli, and multiple enzymatic reactions can mediate its production and degradation. PA acts as a signalling molecule and regulates various cellular processes via its effects on membrane tethering, enzymatic activities of target proteins, and vesicular trafficking. Because of its unique physicochemical properties compared to other phospholipids, PA has emerged as a class of new lipid mediators influencing membrane structure, dynamics, and protein interactions. This review summarizes the biosynthesis, dynamics, and cellular functions and properties of PA.

RAF activation is a key step for signalling through the mitogen-activated protein kinase (MAPK) pathway. The SHOC2 protein, along with MRAS and PP1C, forms a high affinity, heterotrimeric holoenzyme that activates RAF kinases by dephosphorylating a specific phosphoserine. Recently, our research, along with that of three other teams, has uncovered valuable structural and functional insights into the SHOC2-MRAS-PP1C (SMP) holoenzyme complex. In this structural snapshot, we review SMP complex assembly, the dependency on the bound-nucleotide state of MRAS, the substitution of MRAS by the canonical RAS proteins and the roles of SHOC2 and MRAS on PP1C activity and specificity. Furthermore, we discuss the effect of several RASopathy mutations identified within the SMP complex and explore potential therapeutic approaches for targeting the SMP complex in RAS/RAF-driven cancers and RASopathies.

Caveolae are intracellular vesicles with diameters ranging from 50 to 100 nm. The role of caveolins in mediating oxidative stress, autophagy, apoptosis, fibrosis, and vascular remodeling has attracted increasing attention in cardiovascular therapy. Several studies have suggested that caveolin could be a therapeutic target for the treatment of cardiac and/or vascular injury via several pathophysiological mechanisms. Despite substantial advances in our understanding of the basic biology of vesicles over the past decade, the relevance and specific role of these mechanisms in cardiovascular homeostasis remains ambiguous. Here, we review the macroscopic role of caveolins in protecting cardiac function and, at the microscopic level, examine possible cardioprotective caveolar mechanisms, including their antioxidative stress, antiapoptosis, autophagy-regulatory, antifibrosis, and angiogenesis-promoting properties. We believe that the role of caveolins in cardiac functioning has not been fully elucidated and is an important line of future research with several cardioprotective implications.