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Updated: May 12, 2026

Double Labeling Immunofluorescence using Antibodies from the Same Species to Study Host-Pathogen Interactions
Published on: July 10, 2021
The structure of dual-variable-domain immunoglobulin molecules alone and bound to antigen
Ivan Correia1, Joyce Sung2, Randall Burton1
1Protein Analytics; AbbVie Bioresearch Center; Worcester, MA USA.
Abstract:
A dual-specific, tetravalent immunoglobulin G-like molecule, termed dual variable domain immunoglobulin (DVD-Ig™), is engineered to block two targets. Flexibility modulates Fc receptor and complement binding, but could result in undesirable cross-linking of surface antigens and downstream signaling. Understanding the flexibility of parental mAbs is important for designing and retaining functionality of DVD-Ig™ molecules. The architecture and dynamics of a DVD-Ig™ molecule and its parental mAbs was examined using single particle electron microscopy. Hinge angles measured for the DVD-Ig™ molecule were similar to the inner antigen parental mAb. The outer binding domain of the DVD-Ig™ molecule was highly mobile and three-dimensional (3D) analysis showed binding of inner antigen caused the outer domain to fold out of the plane with a major morphological change. Docking high-resolution X-ray structures into the 3D electron microscopy map supports the extraordinary domain flexibility observed in the DVD-Ig™ molecule allowing antigen binding with minimal steric hindrance.
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