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J. Cell Biol.,
Volume 143, Number 6, December 14, 1998 1523-1534
Leukocyte Biology and Inflammation Program, Renal Unit, Department of Medicine, Massachusetts General Hospital and
Harvard Medical School, Charlestown, Massachusetts 02129
In the presence of bound Mn2+, the three-
dimensional structure of the ligand-binding A-domain
from the integrin CR3 (CD11b/CD18) is shown to exist
in the "open" conformation previously described only
for a crystalline Mg2+ complex. The open conformation
is distinguished from the "closed" form by the solvent
exposure of F302, a direct T209-Mn2+ bond, and the
presence of a glutamate side chain in the MIDAS site.
Approximately 10% of wild-type CD11b A-domain is
present in an "active" state (binds to activation-dependent ligands, e.g., iC3b and the mAb 7E3). In the isolated domain and in the holoreceptor, the percentage of
the active form can be quantitatively increased or abolished in F302W and T209A mutants, respectively. The
iC3b-binding site is located on the MIDAS face and includes conformationally sensitive residues that undergo
significant shifts in the open versus closed structures.
We suggest that stabilization of the open structure is independent of the nature of the metal ligand and that
the open conformation may represent the physiologically active form.
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