β-Edge Interactions in a Pentadecameric Human Antibody Vκ Domain

Antibodies are the archetypal molecules of the Ig-fold superfamily. Their highly conserved β-sheet architecture has evolved to avoid aggregation by protecting edge strands. However, the crystal structure of a human Vκ domain described here, reveals an exposed β-edge strand which mediates assembly of a helical pentadecameric oligomer. This edge strand is highly conserved in Vκ domains but is both shortened and capped by the use of two sequential trans-proline residues in Vλ domains. We suggest that the exposure of this β-edge in Vκ domains may explain why light-chain deposition disease is mediated predominantly by κ antibodies.