Title : Crystal
structure of Fcγ receptor I and its implication in high affinity γ-immunoglobulin binding
Abstract :
- Fcγ receptors (FcγRs) play critical roles in humoral and cellular immune responses through interactions with the Fc region of immunoglobulin G ( IgG )
- Among them, FcγRI 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 FcγRI with all three extracellular Ig-like domains (designated as D1, D2, and D3)
- The structure shows that, first, FcγRI has an acute D1-D2 hinge angle similar to that of FcεRI but much smaller than those observed in the low affinity Fcγ receptors
- Second, the D3 domain of FcγRI is position ed away from the putative IgG binding site on the receptor and is thus unlikely to make direct contacts with Fc
- Third, the replacement of FcγRIII FG-loop ((171)LVGSKNV(177)) with that of FcγRI ((171)MGKHRY(176)) resulted in a 15-fold increase in IgG(1 ) binding affinity, whereas a valine insertion in the FcγRI FG-loop ((171)MVGKHRY(177)) abolished the affinity enhancement
- Thus, the FcγRI FG-loop with its conserved one-residue deletion is critical to the high affinity IgG binding
- The structural results support FcγRI 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 FcγRI and provides a structural basis for understanding its physiological function and its therapeutic implication in treating autoimmune diseases
Output (sent_index, trigger,
protein,
sugar,
site):
- 3. FcγRI, , FcγRI, all three extracellular Ig-like domains, -
Output(Part-Of) (sent_index,
protein,
site):
- 1. immunoglobulin G, region
- 5. FcγRI, domain
- 5. FcγRI, position
- 5. IgG, site
- 5. receptor, site
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):