Diverse repertoires of antigen-receptor genes that result from combinatorial splicing of V(D)J gene segments are hallmarks of vertebrate immunity. The (RAG1-RAG2)2 recombinase precisely recognizes and cleaves two different recombination signal sequences (12-RSS and 23-RSS), and forms synaptic complexes only with one 12-RSS and one 23-RSS, a dogma known as the 12/23 rule that governs the recombination fidelity. As described in a recent paper in Cell, the Liao Lab (in collaboration with Dr. Hao Wu's lab at Boston Children's Hospital) used single-particle cryo-electron microscopy (cryo-EM) to determine the structures of synaptic RAG1-RAG2 complexes at up to 3.4 Å resolution. These structures reveal an RSS-induced closed conformation that activates catalysis and uncovers the molecular basis for the 12/23 rule.