3v95

Publication Abstract from PubMed

In the present study, we show that histidines 310 and 435 at the CH2-CH3 interface of the Fc portion of human IgG1 can coordinate a Zn2+ and participate in the control of the CH2-CH2 interdomain opening. Structures obtained in the absence of Zn2+ have a reduced interdomain gap that likely hamper FcgammaR binding. This closed conformation of the Fc is stabilized by inter-CH2 domain sugar contacts. Zinc appears to counteract the sugar mediated constriction, suggesting that zinc could be an important control factor in IgG1/FcgammaR interactions. The results of binding studies performed in the presence of EDTA on FcgammaR expressing cells supports this hypothesis. When a mutated Fc fragment, in which histidines 310 and 435 have been substituted by lysines (Fc H/K), was compared with the wild-type Fc in crystallographic studies, we found that the mutations leave the interface unaltered but have a long-range effect on the CH2 interdomain separation. Moreover, these substitutions have a differential effect on the binding of IgG1 to Fcgamma receptors and their functions. Interaction with the inhibitory FcgammaRIIB is strongly perturbed by the mutations and mutant IgG1 H/K only weakly engages this receptor. By contrast, higher affinity FcgammaR are mostly unaffected.

Effect of zinc on human IgG1 and its FcgammaR interactions.,Siberil S, Menez R, Jorieux S, de Romeuf C, Bourel D, Fridman WH, Ducancel F, Stura EA, Teillaud JL Immunol Lett. 2012 Mar 30;143(1):60-9. PMID:22553781^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.