8YJ8

Characerization of a novel format scFvXVHH single-chain Biparatopic antibody against a metal binding protein, MtsA

Summary for 8YJ8

• Entry DOI: 10.2210/pdb8yj8/pdb
• Descriptor: Iron ABC transporter substrate-binding lipoprotein MtsA, VHH43, ZINC ION, ... (4 entities in total)
• Functional Keywords: antibody, metal transport, metal transport-immune system complex, metal transport/immune system
• Biological source: Streptococcus pyogenes; More
• Total number of polymer chains: 4
• Total formula weight: 91841.88

Authors

Ito, S.,Nagatoishi, S.,Nakakido, M.,Tsumoto, K. (deposition date: 2024-03-01, release date: 2024-06-19, Last modification date: 2024-10-23)

Primary citation

Asano, R.,Takeuchi, M.,Nakakido, M.,Ito, S.,Aikawa, C.,Yokoyama, T.,Senoo, A.,Ueno, G.,Nagatoishi, S.,Tanaka, Y.,Nakagawa, I.,Tsumoto, K.
Characterization of a novel format scFv×VHH single-chain biparatopic antibody against metal binding protein MtsA.
Protein Sci., 33:e5017-e5017, 2024

PubMed Abstract: Biparatopic antibodies (bpAbs) are engineered antibodies that bind to multiple different epitopes within the same antigens. bpAbs comprise diverse formats, including fragment-based formats, and choosing the appropriate molecular format for a desired function against a target molecule is a challenging task. Moreover, optimizing the design of constructs requires selecting appropriate antibody modalities and adjusting linker length for individual bpAbs. Therefore, it is crucial to understand the characteristics of bpAbs at the molecular level. In this study, we first obtained single-chain variable fragments and camelid heavy-chain variable domains targeting distinct epitopes of the metal binding protein MtsA and then developed a novel format single-chain bpAb connecting these fragment antibodies with various linkers. The physicochemical properties, binding activities, complex formation states with antigen, and functions of the bpAb were analyzed using multiple approaches. Notably, we found that the assembly state of the complexes was controlled by a linker and that longer linkers tended to form more compact complexes. These observations provide detailed molecular information that should be considered in the design of bpAbs.

PubMed: 38747382
DOI: 10.1002/pro.5017

Experimental method

X-RAY DIFFRACTION (1.65 Å)