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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.
J Hannan, and
K Young, and
G Szakonyi, and
M J Overduin, and
S J Perkins, and
X Chen, and
V M Holers
February 2010,
Journal of immunology (Baltimore, Md. : 1950),
J Hannan, and
K Young, and
G Szakonyi, and
M J Overduin, and
S J Perkins, and
X Chen, and
V M Holers
July 1985,
The Journal of investigative dermatology,
J Hannan, and
K Young, and
G Szakonyi, and
M J Overduin, and
S J Perkins, and
X Chen, and
V M Holers
January 2016,
Current protein & peptide science,
J Hannan, and
K Young, and
G Szakonyi, and
M J Overduin, and
S J Perkins, and
X Chen, and
V M Holers
June 2001,
Science (New York, N.Y.),
J Hannan, and
K Young, and
G Szakonyi, and
M J Overduin, and
S J Perkins, and
X Chen, and
V M Holers
June 1990,
The Journal of investigative dermatology,
J Hannan, and
K Young, and
G Szakonyi, and
M J Overduin, and
S J Perkins, and
X Chen, and
V M Holers
November 2001,
Journal of immunology (Baltimore, Md. : 1950),
J Hannan, and
K Young, and
G Szakonyi, and
M J Overduin, and
S J Perkins, and
X Chen, and
V M Holers
January 1988,
Annual review of immunology,
J Hannan, and
K Young, and
G Szakonyi, and
M J Overduin, and
S J Perkins, and
X Chen, and
V M Holers
June 1985,
Proceedings of the National Academy of Sciences of the United States of America,
J Hannan, and
K Young, and
G Szakonyi, and
M J Overduin, and
S J Perkins, and
X Chen, and
V M Holers
December 2008,
Journal of molecular biology,
J Hannan, and
K Young, and
G Szakonyi, and
M J Overduin, and
S J Perkins, and
X Chen, and
V M Holers
November 1986,
Molecular immunology,
