Structure of complement receptor (CR) 2 and CR2-C3d complexes.
Using X-ray crystallography, we have determined the structure of the first two short consensus repeats (SCRs) of human complement receptor (CR) 2 in complex with C3d. These studies revealed: (i) a primary site of interaction for C3d within SCR2 of CR2, (ii) a hydrophobic patch holding SCR1 to SCR2 in a rigid V-shape, (iii) a dimer formed by interactions between SCR1 of each molecule, (iv) several non-linear sequences on C3d that interact with CR2 and (v) mutations of C3d amino acids within the co-crystal interface that resulted in decreased binding. In addition, a polymorphism that results in decreased C3d binding and introduces a new glycosylation site predicted to disrupt the dimer interface was found in the New Zealand White autoimmune mouse strain. Although the co-crystal complex results are in agreement with a subset of prior studies, our additional findings, which demonstrate an extended SCR1-SCR2 structure in solution and differences in the kinetics of ligand-receptor interactions with longer forms of CR2, have suggested a more complex receptor-ligand interaction. To characterize this interaction further, several approaches directed at the determination of solution phase interactions as well as the analysis of the three-dimensional structure of CR2 alone and key CR2 mutants will be necessary.
Hannan
J
J
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Young
K
K
Szakonyi
G
G
Overduin
M J
MJ
Perkins
S J
SJ
Chen
X
X
Holers
V M
VM
D000818:Animals; D003167:Complement Activation; D015933:Complement C3d / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D009502:Neutrons; D011485:Protein Binding; D017464:Receptors, Complement 3d / Q000737:chemistry* / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D012542:Scattering, Radiation; D020349:Surface Plasmon Resonance
D008024:Ligands; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D015933:Complement C3d