If you’ve taken a biochemistry class, you’ve probably heard the structure-function paradigm for proteins: amino acid sequence dictates how the protein will be folded, and the ordered 3D structure of the protein is necessary for function.(1) For example, proper formation of an active site is necessary for an enzyme to be able to carry out catalysis. You may have heard some of the models for how proteins fit with their binding partners. For example, the lock-and-key model assumes that the protein and its binding partner are rigid, and this rigid shape determines how well they interact. These models can be useful, but they tend to leave out an important group of proteins: those whose function depends on disorder. Based on sequence analysis, it is estimated that more than 30% of proteins in cells have disordered regions of greater than or equal to 50 consecutive residues.
There are a number of processes that lead to the death of a cell: apoptosis, necrosis, and autophagy are the primary mechanisms – each has a distinct biochemical and morphological fingerprint. In a new paper by Brent Stockwell’s lab at Columbia University (1), the term “ferroptosis” is proposed to describe a process of cell death that doesn’t conform to these fingerprints. In this case, cell death results from an iron-dependent accumulation of lipid reactive oxygen species (ROS).
The group previously identified two structurally-unrelated small molecules, erastin (2) and RSL3 (3), that are selectively lethal to RAS mutant cell lines and named these molecules RAS-selective lethal (RSL) compounds. The underlying driving force for these experiments is that RAS family small GTPases are mutated in a large percentage of cancers (~30%), so compounds that are selectively lethal to RAS mutant cells are needed.
What if I told you there may be a new way of determining whether non-cancerous cells have the potential to form malignancies. If this were possible, it may lead to earlier diagnosis and treatment. The method may sound like a way to see into the future, but it is not fictitious.
Over the last decade scientists have uncovered new evidence in the field of DNA methylation due to advances in technology. DNA methylation is the covalent addition of a methyl group (CH3) at position 5 of the nucleotide base cytosine (see picture below).