Open AccessStructural insights into the interaction of human IgG1 with FcγRI: no direct role of glycans in binding
Author(s) -
Oganesyan Vaheh,
Mazor Yariv,
Yang Chunning,
Cook Kimberly E.,
Woods Robert M.,
Ferguson Andrew,
Bowen Michael A.,
Martin Tom,
Zhu Jie,
Wu Herren,
Dall'Acqua William F.
Publication year - 2015
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s1399004715018015
Subject(s) - glycan , chemistry , immunoglobulin fc fragments , fragment crystallizable region , binding site , plasma protein binding , biophysics , computational biology , antibody , immunoglobulin g , receptor , biology , biochemistry , glycoprotein , genetics
The three‐dimensional structure of a human IgG1 Fc fragment bound to wild‐type human FcγRI is reported. The structure of the corresponding complex was solved at a resolution of 2.4 Å using molecular replacement; this is the highest resolution achieved for an unmutated FcγRI molecule. This study highlights the critical structural and functional role played by the second extracellular subdomain of FcγRI. 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.