PMID: 22553781May 4, 2012Paper

Effect of zinc on human IgG1 and its FcγR interactions

Immunology Letters
Sophie SibérilJean-Luc Teillaud

Abstract

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 FcγR 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/FcγR interactions. The results of binding studies performed in the presence of EDTA on FcγR 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 Fcγ receptors and their functions. Interaction with the inhibitory FcγRIIB is strongly perturbed by the mutations and mutant IgG1 H/K only weakly engages this receptor. By contrast, higher affinity FcγR are mostly unaf...Continue Reading

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Oct 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jonathan M WojciakTom Huxford

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Citations

May 16, 2014·Bulletin of Experimental Biology and Medicine·M A ApresovaS B Cheknev
Jun 12, 2012·MAbs·Frédéric Ducancel, Bruno H Muller
Oct 28, 2019·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Thomas F LerchHugh D Conlon
Aug 13, 2021·Pharmaceutical Research·Shrenik MehtaAlavattam Sreedhara

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