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PDBsum entry 3v8c
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Immune system
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PDB id
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3v8c
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References listed in PDB file
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Key reference
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Title
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Effect of zinc on human igg1 and its fcγr interactions.
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Authors
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S.Sibéril,
R.Ménez,
S.Jorieux,
C.De romeuf,
D.Bourel,
W.H.Fridman,
F.Ducancel,
E.A.Stura,
J.L.Teillaud.
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Ref.
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Immunol Lett, 2012,
143,
60-69.
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PubMed id
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Abstract
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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
unaffected.
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