The saying in the design world is that form follows function. But in biology, and protein biology in particular, it would be more correct to say that form begets function. Shape and structure are the foundation for most protein-based interactions in cells, and are why basic functions like receptor binding, antibody neutralization and gene transcription work.

Two enzymes in the immune system’s B cells, called RAG1 and RAG2, are a perfect example. Together, they form a complex that splices antibody-producing genes together in unique combinations through a process called V(D)J recombination. They do a similar job in T cells to build antigen-binding T-cell receptors (TCRs). In either case, the enzymes are essential to a robust immune response.

In a recent Cell paper, a team led by Hao Wu, PhD, of the Program in Cellular and Molecular Medicine (PCMM) at Boston Children’s Hospital and Maofu Liao, PhD, at Harvard Medical School used electronic microscopy to reveal how RAG1 and 2 interact at a structural level, both with each other and with DNA. The structural biology images they’ve created show plainly what mutations in the genes for these proteins do to cause disease. …