6WIB

Next generation monomeric IgG4 Fc

Summary for 6WIB

• Entry DOI: 10.2210/pdb6wib/pdb
• Descriptor: Immunoglobulin heavy constant gamma 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (4 entities in total)
• Functional Keywords: antibody constant region, fragment crystallizable, mutated, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 25507.53

Authors

Oganesyan, V.Y.,Shan, L.,Dall'Acqua, W.,van Dyk, N. (deposition date: 2020-04-09, release date: 2021-09-15, Last modification date: 2023-10-18)

Primary citation

Shan, L.,Dyk, N.V.,Haskins, N.,Cook, K.M.,Rosenthal, K.L.,Mazor, R.,Dragulin-Otto, S.,Jiang, Y.,Wu, H.,Dall'Acqua, W.F.,Borrok, M.J.,Damschroder, M.M.,Oganesyan, V.
In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance.
Commun Biol, 4:1048-1048, 2021

PubMed Abstract: In a biologic therapeutic landscape that requires versatility in targeting specificity, valency and half-life modulation, the monomeric Fc fusion platform holds exciting potential for the creation of a class of monovalent protein therapeutics that includes fusion proteins and bispecific targeting molecules. Here we report a structure-guided approach to engineer monomeric Fc molecules to adapt multiple versions of half-life extension modifications. Co-crystal structures of these monomeric Fc variants with Fc neonatal receptor (FcRn) shed light into the binding interactions that could serve as a guide for engineering the half-life of antibody Fc fragments. These engineered monomeric Fc molecules also enabled the generation of a novel monovalent bispecific molecular design, which translated the FcRn binding enhancement to improvement of in vivo serum half-life.

PubMed: 34497355
DOI: 10.1038/s42003-021-02565-5

Experimental method

X-RAY DIFFRACTION (2.55 Å)