BACKGROUND: Diabodies are dimeric antibody fragments. In each polypeptide, a heavy-chain variable domain (VH) is linked to a light-chain variable domain (VL) but unlike single-chain Fv fragments, each antigen-binding site is formed by pairing of one VH and one VL domain from the two different polypeptides. Diabodies thus have two antigen-binding sites, and can be bispecific. Direct structural evidence is lacking for the connections and dimeric interactions between the two polypeptides of the diabody. RESULTS: The 2.6 A resolution structure has been determined for a bivalent diabody with a flexible five-residue polypeptide linker between the (amino-terminal) VH and (carboxy-terminal) VL domains. The asymmetric unit of the crystal consists of four polypeptides comprising two diabodies; for one of these polypeptides the linker can be traced between the VH and VL domains. Within each diabody the two associated VH and VL domains make back-to-back interactions through the VH domains, and there is an extensive VL-VL interface between the two diabodies in the asymmetric unit. CONCLUSIONS: The structure of the diabody is very similar to that which had been predicted by molecular modelling. Diabodies directed against cell-surface antigens should be capable of bringing together two cells, such as in cell-targeted therapy, because the two antigen-binding sites of the diabody are at opposite ends of the molecule and separated by approximately 65 A.
BACKGROUND: Diabodies are dimeric antibody fragments. In each polypeptide, a heavy-chain variable domain (VH) is linked to a light-chain variable domain (VL) but unlike single-chain Fv fragments, each antigen-binding site is formed by pairing of one VH and one VL domain from the two different polypeptides. Diabodies thus have two antigen-binding sites, and can be bispecific. Direct structural evidence is lacking for the connections and dimeric interactions between the two polypeptides of the diabody. RESULTS: The 2.6 A resolution structure has been determined for a bivalent diabody with a flexible five-residue polypeptide linker between the (amino-terminal) VH and (carboxy-terminal) VL domains. The asymmetric unit of the crystal consists of four polypeptides comprising two diabodies; for one of these polypeptides the linker can be traced between the VH and VL domains. Within each diabody the two associated VH and VL domains make back-to-back interactions through the VH domains, and there is an extensive VL-VL interface between the two diabodies in the asymmetric unit. CONCLUSIONS: The structure of the diabody is very similar to that which had been predicted by molecular modelling. Diabodies directed against cell-surface antigens should be capable of bringing together two cells, such as in cell-targeted therapy, because the two antigen-binding sites of the diabody are at opposite ends of the molecule and separated by approximately 65 A.
Authors: Joshua S Klein; Priyanthi N P Gnanapragasam; Rachel P Galimidi; Christopher P Foglesong; Anthony P West; Pamela J Bjorkman Journal: Proc Natl Acad Sci U S A Date: 2009-04-16 Impact factor: 11.205
Authors: Xiufeng Wu; Arlene J Sereno; Flora Huang; Steven M Lewis; Ricky L Lieu; Caroline Weldon; Carina Torres; Cody Fine; Micheal A Batt; Jonathan R Fitchett; Andrew L Glasebrook; Brian Kuhlman; Stephen J Demarest Journal: MAbs Date: 2015 Impact factor: 5.857
Authors: Jeffrey V Leyton; Tove Olafsen; Mark A Sherman; Karl B Bauer; Patrick Aghajanian; Robert E Reiter; Anna M Wu Journal: Protein Eng Des Sel Date: 2008-10-28 Impact factor: 1.650
Authors: P Bühler; P Wolf; D Gierschner; I Schaber; A Katzenwadel; W Schultze-Seemann; U Wetterauer; M Tacke; M Swamy; W W A Schamel; U Elsässer-Beile Journal: Cancer Immunol Immunother Date: 2007-06-20 Impact factor: 6.968