TAILIEUCHUNG - Báo cáo khoa học: The association of heavy and light chain variable domains in antibodies: implications for antigen specificity

The antigen-binding site of immunoglobulins is formed by six regions, three from the light and three from the heavy chain variable domains, which, on association of the two chains, form the conventional antigen-binding site of the antibody. | IFEBS Journal The association of heavy and light chain variable domains in antibodies implications for antigen specificity Anna Chailyan1 Paolo Marcatili1 and Anna Tramontano1 2 1 Department of Physics Sapienza University of Rome Italy 2 Istituto Pasteur Fondazione Cenci Bolognetti Sapienza University of Rome Italy Keywords antigen binding immunoglobulins interface structure analysis variable domain packing Correspondence P. Marcatili or A. Tramontano Department of Physics Sapienza University of Rome P. le A. Moro 5 00185 Rome Italy Fax 39 06 4957697 Tel 39 06 49914550 E-mail or These authors contributed equally to this work The antigen-binding site of immunoglobulins is formed by six regions three from the light and three from the heavy chain variable domains which on association of the two chains form the conventional antigenbinding site of the antibody. The mode of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article we analyze the structure of the interface between the heavy and light chain variable domains and show that there are essentially two different modes for their interaction that can be identified by the presence of key amino acids in specific positions of the antibody sequences. We also show that the different packing modes are related to the type of recognized antigen. Received 14 April 2011 revised 2 June 2011 accepted 6 June 2011 doi Introduction Immunoglobulins are multi-chain proteins usually consisting of two pairs of light chains and two pairs of heavy chains with the remarkable exception of heavy chain antibodies which are found in camelids 1 and in a number of fishes 2 3 and are devoid of light chains . In higher vertebrates there are two types of light chain - K and k - whereas heavy chains can

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