title: Structural insights into the interaction of human IgG1 with FcγRI: no direct role of glycans in binding.
abstract: 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.
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Vaheh
authors.initials: V
authors.lastname: Oganesyan
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Yariv
authors.initials: Y
authors.lastname: Mazor
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Chunning
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Cook
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Woods
authors.affiliation: Discovery Sciences, Structure and Biophysics, AstraZeneca Pharmaceuticals, 35 Gatehouse Drive, Mailstop E3, Waltham, MA 02451, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Ferguson
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bowen
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Martin
authors.affiliation: Biopharmaceutical Development, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Herren
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Dall'Acqua
mesh_terms: D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017452:Receptors, IgG / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; D011134:Polysaccharides; D017452:Receptors, IgG
keywords: CD64; Fc receptor; FcγRI; IgG; protein complex