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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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PDB id:
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| Name: |
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Immune system
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Title:
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Crystal structure of monoclonal human anti-rhesus d fc igg1 t125(yb2/0) double mutant (h310 and h435 in k)
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Structure:
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Ig gamma-1 chain c region. Chain: a, b. Fragment: unp residues 119-330. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: human, ighg1. Expressed in: rattus norvegicus. Expression_system_taxid: 10116. Expression_system_cell_line: ebv-transfected b cell crl-1662.
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Resolution:
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2.77Å
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R-factor:
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0.258
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R-free:
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0.316
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Authors:
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R.Menez,E.A.Stura,D.Bourel,S.Siberil,S.Jorieux,C.De Romeuf, F.Ducancel,W.H.Fridman,J.L.Teillaud
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Key ref:
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S.Sibéril
et al.
(2012).
Effect of zinc on human IgG1 and its FcγR interactions.
Immunol Lett,
143,
60-69.
PubMed id:
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Date:
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22-Dec-11
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Release date:
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22-Feb-12
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PROCHECK
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Headers
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References
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P01857
(IGHG1_HUMAN) -
Immunoglobulin heavy constant gamma 1 from Homo sapiens
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Seq:
Struc:
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399 a.a.
212 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 4 residue positions (black
crosses)
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Immunol Lett
143:60-69
(2012)
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PubMed id:
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Effect of zinc on human IgG1 and its FcγR interactions.
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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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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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Links
