3V7M

Crystal structure of monoclonal human anti-Rhesus D Fc IgG1 T125(YB2/0) in the presence of Zn2+

Summary for 3V7M

• Entry DOI: 10.2210/pdb3v7m/pdb
• Related: 2J6E 3D6G 3FJT 3V8C
• Descriptor: Ig gamma-1 chain C region, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (6 entities in total)
• Functional Keywords: fc igg1, fc-gamma receptor, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P01857
• Total number of polymer chains: 1
• Total formula weight: 25666.65

Authors

Menez, R.,Stura, E.A.,Bourel, D.,Siberil, S.,Jorieux, S.,De Romeuf, C.,Ducancel, F.,Fridman, W.H.,Teillaud, J.L. (deposition date: 2011-12-21, release date: 2012-02-22, Last modification date: 2024-11-20)

Primary citation

Siberil, S.,Menez, R.,Jorieux, S.,de Romeuf, C.,Bourel, D.,Fridman, W.H.,Ducancel, F.,Stura, E.A.,Teillaud, J.L.
Effect of zinc on human IgG1 and its Fc gamma R interactions.
Immunol.Lett., 143:60-69, 2012

PubMed 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 unaffected.

PubMed: 22553781

Experimental method

X-RAY DIFFRACTION (2.02 Å)