Evidence for plasticity and structural mimicry at the immunoglobulin light chain-protein L interface.
The multidomain bacterial surface protein L (PpL) is a virulence factor expressed by only 10% of Peptostreptococcus magnus strains, and its expression is correlated with bacterial vaginosis. The molecular basis for its ability to recognize 60% of mammalian immunoglobulin light chain variable regions (V(L)) has been described recently by x-ray crystallography, which suggested the presence of two V(L) binding sites on each protein L domain (Graille, M., Stura, E. A., Housden, N. G., Beckingham, J. A., Bottomley, S. P., Beale, D., Taussig, M. J., Sutton, B. J., Gore, M. G., and Charbonnier, J. (2001) Structure 9, 679-687). Here, we report the crystal structure at 2.1 A resolution of a protein L mutant complexed to an Fab' fragment with only 50% of the V(L) residues interacting with PpL site 1 conserved. Comparison of the site 1 interface from both structures shows how protein L is able to accommodate these sequence differences and therefore bind to a large repertoire of Ig. The x-ray structure and NMR results confirm the existence of two V(L) binding sites on a single protein L domain. These sites exhibit a remarkable structural mimicry of growth factors binding to their receptors. This could explain the protein L superantigenic activity on human B lymphocytes.
Graille
Marc
M
Laboratoire de Structure des Protéines, Département d'Ingénierie et d'Etudes des Protéines (DIEP), Commissariat à l'Energie Atomique, Centre d'Etudes de Saclay, Gif-sur-Yvette, France.
Harrison
Steven
S
Crump
Matthew P
MP
Findlow
Stuart C
SC
Housden
Nicholas G
NG
Muller
Bruno H
BH
Battail-Poirot
Nicole
N
Sibaï
Geneviève
G
Sutton
Brian J
BJ
Taussig
Michael J
MJ
Jolivet-Reynaud
Colette
C
Gore
Michael G
MG
Stura
Enrico A
EA
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry; D001402:B-Lymphocytes / Q000378:metabolism; D001426:Bacterial Proteins; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D007147:Immunoglobulin Light Chains / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010462:Peptostreptococcus / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D000906:Antibodies; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D007147:Immunoglobulin Light Chains; C116593:L-protein, Peptococcus magnus