THE β, γ-crystallins form a class of homologous proteins in the eye lens. Each γ-crystallin comprises four topologically equivalent, Greek key motifs; pairs of motifs are organized around a local dyad to give domains and two similar domains are in turn related by a further local dyad1–4. Sequence comparisons and model building predicted that hetero-oligomeric β-crystallins also had internally quadruplicated subunits, but with extensions at the N and C termini, indicating that β, γ-crystallins evolved in two duplication steps from an ancestral protein folded as a Greek key5–7. We report here the X-ray analysis at 2.1 Å resolution of βB2-crystall in homodimer which shows that the connecting peptide is extended and the two domains separated in a way quite unlike γ-crystallin. Domain interactions analogous to those within monomeric γ-crystallin are intermolecular and related by a crystallographic dyad in the βB2-crystallin dimer. This shows how oligomers can evolve by conserving an interface rather than connectivity. A further interaction between dimers suggests a model for more complex aggregates of β-crystallin in the len
