Beta-edge interactions in a pentadecameric human antibody V kappa domain.
Antibodies are the archetypal molecules of the Ig-fold superfamily. Their highly conserved beta-sheet architecture has evolved to avoid aggregation by protecting edge strands. However, the crystal structure of a human V kappa domain described here, reveals an exposed beta-edge strand which mediates assembly of a helical pentadecameric oligomer. This edge strand is highly conserved in V kappa domains but is both shortened and capped by the use of two sequential trans-proline residues in V lambda domains. We suggest that the exposure of this beta-edge in V kappa domains may explain why light-chain deposition disease is mediated predominantly by kappa antibodies.
James
Leo C
LC
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK. lcj@mrc-lmb.cam.ac.uk
Jones
Phil C
PC
McCoy
Airlie
A
Tennent
Glenys A
GA
Pepys
Mark B
MB
Famm
Kristoffer
K
Winter
Greg
G
D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry*; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains