Structural insights into the interactions between human IgE and its high affinity receptor FcεRI

被引:28
作者
Wurzburg, BA
Jardetzky, TS
机构
[1] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA
[2] Northwestern Univ, Dept Microbiol & Immunol, Evanston, IL 60208 USA
基金
美国国家卫生研究院;
关键词
IgE; Fc receptor; Fc epsilon RI; antibody; X-ray crystallography; allergy; asthma; mast cell; structure; drug design; Fe; signal;
D O I
10.1016/S0161-5890(02)00035-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The interaction of IgE antibodies with the high affinity IgE receptor. FcepsilonRI. is a key step in the initiation of anti-parasitic immunity and allergic reactions, Recent structural Studies of the receptor, the IgE-Fe and the IgE-Fe:FcepsilonRI complex hake revealed how these two proteins interact to prime mast cell responses to antigen. The structures have revealed a novel arrangement for the FcepsilonRl ectodomains that is also observed in homologous members of this antibody receptor family. The crystal Structure of the IgE-Fe:FcepsilonRl complex clarified how a 1:1 complex between the antibody and receptor is formed, with the receptor binding each chain of the antibody Fe dimer. The IgE-Fe Structure in the absence of the receptor revealed the potential for large conformational rearrangements within the IgE that may affect receptor binding. These studies provide the basis, for further investigation of the specificity of anti body : receptor binding and for the development of new treatments for allergic hpersensitivities. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1063 / 1072
页数:10
相关论文
共 69 条
[51]   SOLUBLE HUMAN HIGH-AFFINITY RECEPTOR FOR IGE ABROGATES THE IGE-MEDIATED ALLERGIC REACTION [J].
RA, C ;
KUROMITSU, S ;
HIROSE, T ;
YASUDA, S ;
FURUICHI, K ;
OKUMURA, K .
INTERNATIONAL IMMUNOLOGY, 1993, 5 (01) :47-54
[52]   The structure of a human type III Fcγ receptor in complex with Fc [J].
Radaev, S ;
Motyka, S ;
Fridman, WH ;
Sautes-Fridman, C ;
Sun, PD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (19) :16469-16477
[53]   3-DIMENSIONAL STRUCTURE OF THE MCG IGG1 IMMUNOGLOBULIN [J].
RAJAN, SS ;
ELY, KR ;
ABOLA, EE ;
WOOD, MK ;
COLMAN, PM ;
ATHAY, RJ ;
EDMUNDSON, AB .
MOLECULAR IMMUNOLOGY, 1983, 20 (07) :787-799
[54]  
ROBERTSON MW, 1993, J BIOL CHEM, V268, P12736
[55]  
Saini SS, 1999, J IMMUNOL, V162, P5624
[56]   CRYSTAL-STRUCTURE OF THE C2 FRAGMENT OF STREPTOCOCCAL PROTEIN-G IN COMPLEX WITH THE FC DOMAIN OF HUMAN-IGG [J].
SAUERERIKSSON, AE ;
KLEYWEGT, GJ ;
UHL, M ;
JONES, TA .
STRUCTURE, 1995, 3 (03) :265-278
[57]   Amino acid residues that influence FcεRI-mediated effector functions of human immunoglobulin E [J].
Sayers, I ;
Cain, SA ;
Swan, JRM ;
Pickett, MA ;
Watt, PJ ;
Holgate, ST ;
Padlan, EA ;
Schuck, P ;
Helm, BA .
BIOCHEMISTRY, 1998, 37 (46) :16152-16164
[58]   RECEPTOR PHAGE - DISPLAY OF FUNCTIONAL DOMAINS OF THE HUMAN HIGH-AFFINITY IGE RECEPTOR ON THE M13 PHAGE SURFACE [J].
SCARSELLI, E ;
ESPOSITO, G ;
TRABONI, C .
FEBS LETTERS, 1993, 329 (1-2) :223-226
[59]   The 3.2-Å crystal structure of the human IgG1 Fc fragment-FcγRIII complex [J].
Sondermann, P ;
Huber, R ;
Oosthuizen, V ;
Jacob, U .
NATURE, 2000, 406 (6793) :267-273
[60]   Crystal structure of the soluble form of the human Fcγ-receptor IIb:: a new member of the immunoglobulin superfamily at 1.7 Å resolution [J].
Sondermann, P ;
Huber, R ;
Jacob, U .
EMBO JOURNAL, 1999, 18 (05) :1095-1103