3C2S

Structural Characterization of a Human Fc Fragment Engineered for Lack of Effector Functions

Summary for 3C2S

• Entry DOI: 10.2210/pdb3c2s/pdb
• Descriptor: IGHM protein, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]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: fc fragment, mutant, effector function, receptor, protein binding, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 27295.81

Authors

Oganesyan, V.,Wu, H.,Dall'Acqua, W.F. (deposition date: 2008-01-25, release date: 2008-08-19, Last modification date: 2024-10-16)

Primary citation

Oganesyan, V.,Gao, C.,Shirinian, L.,Wu, H.,Dall'Acqua, W.F.
Structural characterization of a human Fc fragment engineered for lack of effector functions.
Acta Crystallogr.,Sect.D, 64:700-704, 2008

PubMed Abstract: The first three-dimensional structure of a human Fc fragment genetically engineered for the elimination of its ability to mediate antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity is reported. When introduced into the lower hinge and CH2 domain of human IgG1 molecules, the triple mutation L234F/L235E/P331S ('TM') causes a profound decrease in their binding to human CD64, CD32A, CD16 and C1q. Enzymatically produced Fc/TM fragment was crystallized and its structure was solved at a resolution of 2.3 A using molecular replacement. This study revealed that the three-dimensional structure of Fc/TM is very similar to those of other human Fc fragments in the experimentally visible region spanning residues 236-445. Thus, the dramatic broad-ranging effects of TM on IgG binding to several effector molecules cannot be explained in terms of major structural rearrangements in this portion of the Fc.

PubMed: 18560159
DOI: 10.1107/S0907444908007877

Experimental method

X-RAY DIFFRACTION (2.3 Å)