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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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References listed in PDB file
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Key reference
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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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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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Ref.
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Mabs, 2013,
5,
358-363.
[DOI no: ]
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PubMed id
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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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