Crystal structure of an intact human IgG: antibody asymmetry, flexibility, and a guide for HIV-1 vaccine design

Saphire, Erica Ollmann, Stanfield, Robyn L., Crispin, Max, Morris, Garrett, Zwick, Michael B., Pantophlet, Ralph A., Parren, Paul W H I, Rudd, Pauline M., Dwek, Raymond A., Burton, Dennis R. and Wilson, Ian A. (2003) Crystal structure of an intact human IgG: antibody asymmetry, flexibility, and a guide for HIV-1 vaccine design. In, Axford, John S. (ed.) Glycobiology and Medicine: Conference Proceedings. (Advances in Experimental Medicine and Biology, 535) Boston. Springer, pp. 55-66. (doi:10.1007/978-1-4615-0065-0_4).

Abstract

Antibodies link antigen and immunological effector systems through the use of highly flexible linkers that connect the hypervariable antigen binding sites (Fabs) to the effector domain (Fc). The extensive flexibility of the antibody molecule permits antibodies to adapt to a vast array of antigen shapes and sizes while retaining a covalent link between the Fab domains and the conserved Fc region that interacts with a limited number of effector systems, such as Fc receptor and complement (Burton, 1985; Burton, 1990). However, this inherent molecular flexibility of intact antibodies has hindered their crystallization. Although over 200 structures of antibody fragments, mainly Fab and Fab’ fragments, have been determined, entire structures of IgGs with full length hinges have only been reported three times: two structures of murine mAbs (Harris et al., 1995; Harris et al., 1997) and now the structure of human IgG1 bl2, directed against HIV-1 gp120 (Saphire et al., 2001a; Saphire et al., 2001b). The structure of IgG1 b12 represents the first structure of an intact human antibody with a full-length hinge for which all domains are visible in the electron density map.

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Contributors

Author: Max Crispin

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