Structural basis for binding of human IgG1 to its high-affinity human receptor Fc?RI.

ABSTRACT: Cell-surface Fc? receptors mediate innate and adaptive immune responses. Human Fc? receptor I (hFc?RI) binds IgGs with high affinity and is the only Fc? receptor that can effectively capture monomeric IgGs. However, the molecular basis of hFc?RI's interaction with Fc has not been determined, limiting our understanding of this major immune receptor. Here we report the crystal structure of a complex between hFc?RI and human Fc, at 1.80?Å resolution, revealing an unique hydrophobic pocket at the surface of hFc?RI perfectly suited for residue Leu235 of Fc, which explains the high affinity of this complex. Structural, kinetic and thermodynamic data demonstrate that the binding mechanism is governed by a combination of non-covalent interactions, bridging water molecules and the dynamic features of Fc. In addition, the hinge region of hFc?RI-bound Fc adopts a straight conformation, potentially orienting the Fab moiety. These findings will stimulate the development of novel therapeutic strategies involving hFc?RI.

SUBMITTER: Kiyoshi M 

PROVIDER: S-EPMC4423232 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature