4HJJ

Structure Reveals Function of the Dual Variable Domain Immunoglobulin (DVD-Ig) Molecule

Summary for 4HJJ

• Entry DOI: 10.2210/pdb4hjj/pdb
• Related: 2VXV
• Descriptor: Interleukin-18, Anti-IL12 Anti-IL18 DFab Heavy Chain, Anti-IL12 Anti-IL18 DFab Light Chain, ... (7 entities in total)
• Functional Keywords: dfab complex, il-18, dual variable domain immunoglobulin, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: Q14116
• Total number of polymer chains: 3
• Total formula weight: 91905.16

Authors

Jakob, C.G.,Edalji, R.,Judge, R.A.,DiGiammarino, E.,Li, Y.,Gu, J.,Ghayur, T. (deposition date: 2012-10-12, release date: 2013-05-08, Last modification date: 2024-11-20)

Primary citation

Jakob, C.G.,Edalji, R.,Judge, R.A.,Digiammarino, E.,Li, Y.,Gu, J.,Ghayur, T.
Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig[TM]) molecule
MAbs, 5:358-363, 2013

PubMed Abstract: 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.

PubMed: 23549062
DOI: 10.4161/mabs.23977

Experimental method

X-RAY DIFFRACTION (2.1 Å)