Harrison P T, Allen J M
Department of Medicine and Therapeutics, The University of Glasgow, UK.
Protein Eng. 1998 Mar;11(3):225-32. doi: 10.1093/protein/11.3.225.
The high affinity IgG receptor, FcgammaRI, is comprised of three immunoglobulin superfamily (IgSF) domains (EC1, EC2 and EC3), a single transmembrane spanning region, and a short cytoplasmic tail. We have shown a role for three separate domains of FcgammaRI in the high affinity binding of IgG. Affinity measurements of chimeric FcgammaRs in which EC1 and EC2 of FcgammaRI have been replaced with the homologous EC1 and/or EC2 domains of the low affinity IgG receptor, FcgammaRII indicate that both EC2 and EC3 are essential for high affinity binding of monomeric IgG. Identification of EC3 from FcgammaRI as the binding site for the monoclonal antibody 10.1, which blocks IgG binding, provides further evidence for the role of this domain in binding. In addition, we have found that the affinity of FcgammaRI is increased threefold when co-expressed with its accessory molecule, gamma-chain. Affinity measurements of further chimeras indicates that the transmembrane domain of FcgammaRI has a negative influence upon the affinity of the receptor. To account for these observations, we propose that receptor dimerization is required for maximal affinity of FcgammaRI. Dimerization may serve as the mechanism by which IgG binding triggers several FcgammaRI-mediated events.
高亲和力IgG受体FcγRI由三个免疫球蛋白超家族（IgSF）结构域（EC1、EC2和EC3）、一个单一跨膜区和一个短细胞质尾组成。我们已经证明FcγRI的三个独立结构域在IgG的高亲和力结合中发挥作用。对嵌合FcγR进行亲和力测量，其中FcγRI的EC1和EC2已被低亲和力IgG受体FcγRII的同源EC1和/或EC2结构域取代，结果表明EC2和EC3对于单体IgG的高亲和力结合都是必不可少的。将FcγRI的EC3鉴定为阻断IgG结合的单克隆抗体10.1的结合位点，为该结构域在结合中的作用提供了进一步的证据。此外，我们发现FcγRI与其辅助分子γ链共表达时，其亲和力增加了三倍。对进一步嵌合体的亲和力测量表明，FcγRI的跨膜结构域对受体的亲和力有负面影响。为了解释这些观察结果，我们提出FcγRI的最大亲和力需要受体二聚化。二聚化可能是IgG结合触发几种FcγRI介导事件的机制。
