Structural insights into the interaction of human IgG1 with FcγRI: no direct role of glycans in binding

The three-dimensional structure of a human IgG1 Fc fragment bound to wildtype human Fc gamma RI is reported. The structure of the corresponding complex was solved at a resolution of 2.4 angstrom using molecular replacement; this is the highest resolution achieved for an unmutated Fc gamma RI molecule. This study highlights the critical structural and functional role played by the second extracellular subdomain of Fc gamma RI. It also explains the long-known major energetic contribution of the Fc 'LLGG' motif at positions 234-237, and particularly of Leu235, via a 'lock- and-key' mechanism. Finally, a previously held belief is corrected and a differing view is offered on the recently proposed direct role of Fc carbohydrates in the corresponding interaction. Structural evidence is provided that such glycan-related effects are strictly indirect.