4W4O

High-resolution crystal structure of Fc bound to its human receptor Fc-gamma-RI

Summary for 4W4O

• Entry DOI: 10.2210/pdb4w4o/pdb
• Related: 4W4N
• Descriptor: Ig gamma-1 chain C region, High affinity immunoglobulin gamma Fc receptor I, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: immune complex igg1 protein-protein complex asymmetry, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 87850.19

Authors

Caaveiro, J.M.M.,Kiyoshi, M.,Tsumoto, K. (deposition date: 2014-08-15, release date: 2015-04-29, Last modification date: 2024-11-06)

Primary citation

Kiyoshi, M.,Caaveiro, J.M.M.,Kawai, T.,Tashiro, S.,Ide, T.,Asaoka, Y.,Hatayama, K.,Tsumoto, K.
Structural basis for binding of human IgG1 to its high-affinity human receptor Fc gamma RI
Nat Commun, 6:6866-6866, 2015

PubMed Abstract: 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.

PubMed: 25925696
DOI: 10.1038/ncomms7866

Experimental method

X-RAY DIFFRACTION (1.8 Å)