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PDBsum entry 4hjj
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Immune system
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PDB id
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4hjj
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Contents |
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157 a.a.
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341 a.a.
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327 a.a.
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PDB id:
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Immune system
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Title:
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Structure reveals function of the dual variable domain immunoglobulin (dvd-ig) molecule
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Structure:
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Interleukin-18. Chain: a. Fragment: unp resiudes 37-192. Synonym: il-18, iboctadekin, interferon gamma-inducing factor, ifn- gamma-inducing factor, interleukin-1 gamma, il-1 gamma. Engineered: yes. Anti-il12 anti-il18 dfab heavy chain. Chain: h. Engineered: yes.
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: il18, igif, il1f4. Expressed in: escherichia coli. Expression_system_taxid: 562. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_taxid: 9606
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Resolution:
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2.10Å
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R-factor:
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0.186
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R-free:
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0.220
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Authors:
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C.G.Jakob,R.Edalji,R.A.Judge,E.Digiammarino,Y.Li,J.Gu,T.Ghayur
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Key ref:
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C.G.Jakob
et al.
(2013).
Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig™) molecule.
Mabs,
5,
358-363.
PubMed id:
DOI:
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Date:
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12-Oct-12
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Release date:
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08-May-13
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PROCHECK
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Headers
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References
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Q14116
(IL18_HUMAN) -
Interleukin-18 from Homo sapiens
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Seq:
Struc:
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193 a.a.
157 a.a.*
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DOI no:
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Mabs
5:358-363
(2013)
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PubMed id:
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Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig™) molecule.
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C.G.Jakob,
R.Edalji,
R.A.Judge,
E.DiGiammarino,
Y.Li,
J.Gu,
T.Ghayur.
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ABSTRACT
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Several bispecific antibody-based formats have been developed over the past 25
years in an effort to produce a new generation of immunotherapeutics that target
two or more disease mechanisms simultaneously. One such format, the
dual-variable domain immunoglobulin (DVD-Ig™), combines the target binding
domains of two monoclonal antibodies via flexible naturally occurring linkers,
which yields a tetravalent IgG - like molecule. We report the structure of an
interleukin (IL)12-IL18 DVD-Ig™ Fab (DFab) fragment with IL18 bound to the
inner variable domain (VD) that reveals the remarkable flexibility of the
DVD-Ig™ molecule and how the DVD-Ig™ format can function to bind four
antigens simultaneously. An understanding of how the inner variable domain
retains function is of critical importance for designing DVD-Ig™ molecules,
and for better understanding of the flexibility of immunoglobulin variable
domains and linkers, which may aid in the design of improved bi- and
multi-specific biologics in general.
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Links
