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PDBsum entry 4j12
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Immune system
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PDB id
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4j12
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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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Monomeric fc
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Structure:
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Human fc fragment. Chain: a. Fragment: unp residues 137-345. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293
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Resolution:
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1.90Å
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R-factor:
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0.223
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R-free:
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0.238
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Authors:
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T.Ishino,M.Wang,L.Mosyak,A.Tam,W.Duan,K.Svenson,A.Joyce,D.O'Hara, L.Lin,W.Somers,R.Kriz
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Key ref:
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T.Ishino
et al.
(2013).
Engineering a monomeric Fc domain modality by N-glycosylation for the half-life extension of biotherapeutics.
J Biol Chem,
288,
16529-16537.
PubMed id:
DOI:
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Date:
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31-Jan-13
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Release date:
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01-May-13
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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.
209 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 5 residue positions (black
crosses)
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DOI no:
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J Biol Chem
288:16529-16537
(2013)
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PubMed id:
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Engineering a monomeric Fc domain modality by N-glycosylation for the half-life extension of biotherapeutics.
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T.Ishino,
M.Wang,
L.Mosyak,
A.Tam,
W.Duan,
K.Svenson,
A.Joyce,
D.M.O'Hara,
L.Lin,
W.S.Somers,
R.Kriz.
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ABSTRACT
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Human IgG is a bivalent molecule that has two identical Fab domains connected by
a dimeric Fc domain. For therapeutic purposes, however, the bivalency of IgG and
Fc fusion proteins could cause undesired properties. We therefore engineered the
conversion of the natural dimeric Fc domain to a highly soluble monomer by
introducing two Asn-linked glycans onto the hydrophobic CH3-CH3 dimer interface.
The monomeric Fc (monoFc) maintained the binding affinity for neonatal Fc
receptor (FcRn) in a pH-dependent manner. We solved the crystal structure of
monoFc, which explains how the carbohydrates can stabilize the protein surface
and provides the rationale for molecular recognition between monoFc and FcRn.
The monoFc prolonged the in vivo half-life of an antibody Fab domain, and a
tandem repeat of the monoFc further prolonged the half-life. This monoFc
modality can be used to improve the pharmacokinetics of monomeric therapeutic
proteins with an option to modulate the degree of half-life extension.
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Links
