3rjd
Crystal structure of Fc RI and its implication to high affinity immunoglobulin G binding
Structural highlights
FunctionFCGR1_HUMAN High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.[1] [2] [3] [4] Publication Abstract from PubMedFcgamma receptors (FcgammaRs) play critical roles in humoral and cellular immune responses through interactions with the Fc region of immunoglobulin G (IgG). Among them, FcgammaRI is the only high affinity receptor for IgG and thus is a potential target for immunotherapy. Here we report the first crystal structure of an FcgammaRI with all three extracellular Ig-like domains (designated as D1, D2, and D3). The structure shows that, first, FcgammaRI has an acute D1-D2 hinge angle similar to that of FcepsilonRI but much smaller than those observed in the low affinity Fcgamma receptors. Second, the D3 domain of FcgammaRI is positioned away from the putative IgG binding site on the receptor and is thus unlikely to make direct contacts with Fc. Third, the replacement of FcgammaRIII FG-loop ((171)LVGSKNV(177)) with that of FcgammaRI ((171)MGKHRY(176)) resulted in a 15-fold increase in IgG(1) binding affinity, whereas a valine insertion in the FcgammaRI FG-loop ((171)MVGKHRY(177)) abolished the affinity enhancement. Thus, the FcgammaRI FG-loop with its conserved one-residue deletion is critical to the high affinity IgG binding. The structural results support FcgammaRI binding to IgG in a similar mode as its low affinity counterparts. Taken together, our study suggests a molecular mechanism for the high affinity IgG recognition by FcgammaRI and provides a structural basis for understanding its physiological function and its therapeutic implication in treating autoimmune diseases. Crystal structure of Fcgamma receptor I and its implication in high affinity gamma-immunoglobulin binding.,Lu J, Ellsworth JL, Hamacher N, Oak SW, Sun PD J Biol Chem. 2011 Nov 25;286(47):40608-13. Epub 2011 Sep 29. PMID:21965667[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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