Figure 4
From: Structural insights into the bi-specific cross-over dual variable antibody architecture by cryo-EM
Model explaining the observed 1:1 stoichiometry for IL13: antigen CODVIg: The structural flexibility of Fc domain evident from our cryo-EM studies of full antibody CODVIg results in an inclination of the Fc domain relative to the Fab domains. This would occlude, depending on Fc orientation, one of the CODVIg binding sites. However, it cannot be discounted that structural rearrangements in the Fab domains, induced due to antigen binding (IL4 or IL13), can be translated to Fc domain via the hinge region to induce additional flexibility to Fc, which, for reasons yet unknown, hinders the binding of IL13 to both Fabs simultaneously.
