PDBsum entry 4w4o

Immune system

PDB id: 4w4o

Contents

Protein chains

215 a.a.

259 a.a.

Ligands

NAG-NAG-BMA-MAN-NAG-GAL-MAN-NAG-FUC ×2

NAG-NAG

NAG-NAG-BMA-MAN-MAN-MAN

ACT ×9

GOL ×2

Metals

_ZN ×6

Waters ×572

PDB id:

4w4o

Name:

Immune system

Title:

High-resolution crystal structure of fc bound to its human receptor fc-gamma-ri

Structure:

Ig gamma-1 chain c region. Chain: a, b. Fragment: unp residues 107-330. Engineered: yes. High affinity immunoglobulin gamma fc receptor i. Chain: c. Fragment: unp residues 16-289. Synonym: igg fc receptor i, fc-gamma ri, fcri, fc-gamma ria, fcgammaria.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ighg1. Other_details: the protein is commercially purchased from roche.. Gene: fcgr1a, fcg1, fcgr1, igfr1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

1.80Å R-factor: 0.175 R-free: 0.215

Authors:

J.M.M.Caaveiro,M.Kiyoshi,K.Tsumoto

Key ref:

M.Kiyoshi et al. (2015). Structural basis for binding of human IgG1 to its high-affinity human receptor FcγRI. Nat Commun, 6, 6866. PubMed id: 25925696 DOI: 10.1038/ncomms7866

Date:

15-Aug-14 Release date: 29-Apr-15

Protein chains

P01857  (IGHG1_HUMAN) -  Immunoglobulin heavy constant gamma 1 from Homo sapiens

Seq: 399 a.a.

Struc: 215 a.a.*

Protein chain

P12314  (FCGR1_HUMAN) -  High affinity immunoglobulin gamma Fc receptor I from Homo sapiens

Seq: 374 a.a.

Struc: 259 a.a.*

* PDB and UniProt seqs differ at 17 residue positions (black crosses)

DOI no: 10.1038/ncomms7866

Nat Commun 6:6866 (2015)

PubMed id: 25925696

Structural basis for binding of human IgG1 to its high-affinity human receptor FcγRI.

M.Kiyoshi, J.M.Caaveiro, T.Kawai, S.Tashiro, T.Ide, Y.Asaoka, K.Hatayama, K.Tsumoto.

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.