人类白细胞Fc受体FcγRIIa的晶体结构。

Crystal structure of the human leukocyte Fc receptor, Fc gammaRIIa.

作者信息

Maxwell K F, Powell M S, Hulett M D, Barton P A, McKenzie I F, Garrett T P, Hogarth P M

机构信息

Biomolecular Research Institute, Parkville, Victoria, Australia.

出版信息

Nat Struct Biol. 1999 May;6(5):437-42. doi: 10.1038/8241.

DOI:10.1038/8241

PMID:10331870

Abstract

Fc gamma receptors bind IgG to initiate cellular responses against pathogens and soluble antigens. We have determined the three-dimensional structure of the extracellular portion of human Fc gammaRIIa to 2.0 A resolution providing a structural basis for the unique functions of the leukocyte FcR family. The receptor is composed of two immunoglobulin domains and arranged to expose the ligand-binding site at one end of domain 2. Using alanine mutants we find that the binding sites for IgG1 and 2 are similar but the relative importance of specific regions on the receptor varies. In crystals, Fc gammaRIIa molecules associate to resemble V(L)V(H) dimers, suggesting that two Fc gammaRIIa molecules could cooperate to bind IgG in an asymmetric manner.

摘要

Fcγ受体结合IgG以启动针对病原体和可溶性抗原的细胞反应。我们已确定人FcγRIIa细胞外部分的三维结构，分辨率达2.0埃，为白细胞FcR家族的独特功能提供了结构基础。该受体由两个免疫球蛋白结构域组成，其排列方式使得结构域2一端暴露配体结合位点。利用丙氨酸突变体，我们发现IgG1和IgG2的结合位点相似，但受体上特定区域的相对重要性有所不同。在晶体中，FcγRIIa分子缔合形成类似V(L)V(H)二聚体的结构，这表明两个FcγRIIa分子可能以不对称方式协同结合IgG。