TY - JOUR
T1 - Structural basis for binding of human IgG1 to its high-affinity human receptor FcγRI
AU - Kiyoshi, Masato
AU - Caaveiro, Jose M.M.
AU - Kawai, Takeaki
AU - Tashiro, Shinya
AU - Ide, Teruhiko
AU - Asaoka, Yoshiharu
AU - Hatayama, Kouta
AU - Tsumoto, Kouhei
N1 - Funding Information:
Access to beamline BL-5A was granted by the Photon Factory Advisory Committee (Proposals 2009G040 and 2012G191). We thank Yuji Watanabe for expert advice with the baculovirus expression system. This work has been financed by a grant from the Ministry of Economy, Trade and Industry of Japan.
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/4/30
Y1 - 2015/4/30
N2 - Cell-surface Fcγ receptors mediate innate and adaptive immune responses. Human Fcγ receptor I (hFcγRI) binds IgGs with high affinity and is the only Fcγ receptor that can effectively capture monomeric IgGs. However, the molecular basis of hFcγRI'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 hFcγRI and human Fc, at 1.80 Å resolution, revealing an unique hydrophobic pocket at the surface of hFcγRI 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 hFcγRI-bound Fc adopts a straight conformation, potentially orienting the Fab moiety. These findings will stimulate the development of novel therapeutic strategies involving hFcγRI.
AB - Cell-surface Fcγ receptors mediate innate and adaptive immune responses. Human Fcγ receptor I (hFcγRI) binds IgGs with high affinity and is the only Fcγ receptor that can effectively capture monomeric IgGs. However, the molecular basis of hFcγRI'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 hFcγRI and human Fc, at 1.80 Å resolution, revealing an unique hydrophobic pocket at the surface of hFcγRI 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 hFcγRI-bound Fc adopts a straight conformation, potentially orienting the Fab moiety. These findings will stimulate the development of novel therapeutic strategies involving hFcγRI.
UR - http://www.scopus.com/inward/record.url?scp=84928776106&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928776106&partnerID=8YFLogxK
U2 - 10.1038/ncomms7866
DO - 10.1038/ncomms7866
M3 - Article
C2 - 25925696
AN - SCOPUS:84928776106
SN - 2041-1723
VL - 6
JO - Nature communications
JF - Nature communications
M1 - 6866
ER -