3V7M: Crystal Structure Of Monoclonal Human Anti-rhesus D Fc Igg1 T125(yb2/0) In The Presence Of Zn2+

Citation:
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 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.
PDB ID: 3V7MDownload
MMDB ID: 97467
PDB Deposition Date: 2011/12/21
Updated in MMDB: 2014/10
Experimental Method:
x-ray diffraction
Resolution: 2.02  Å
Source Organism:
Similar Structures:
Biological Unit for 3V7M: dimeric; determined by author and by software (PISA)
Molecular Components in 3V7M
Label Count Molecule
Proteins (2 molecules)
2
IG Gamma-1 Chain C Region(Gene symbol: IGHG1)
Molecule annotation
Chemicals (28 molecules)
1
6
2
6
3
2
4
6
5
6
6
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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