Concanavalin A

Abstract

Lectins have been widely used to analyze a variety of fundamental processes in cell biology. Along with our studies on the cell surface and mitosis, we have determined the amino acid sequence and three-dimensional structure of concanavalin A (Con A), the mitogenic lectin from Canavalia. Knowledge of the structure has been useful in interpreting experiments on lymphocyte mitogenesis and the effects of Con A on cell surface receptor motility. Con A subunits for a molecular weight of 25,500 fold into dome-shaped structures of maximum dimensions of 42 x 40 x 39 A. The domes are related by 222 symmetry to form approximately tetrahedral tetramers.

Each subunit contains two large antiparallel folded sheets, and the subunits join to form dimers and tetramers through interactions involving one of these folded sheets. We have examined the binding of a variety of carbohydrates to Con A and have obtained preliminary data suggesting that there are differences in the saccharide binding behaviour of Concanavalin A in solution and in the crystalline state. Dimeric chemical derivatives of Con A have been prepared and have been shown to have different biological activities from the native tetrameric protein. Under different conditions, native Con A exhibits two antagonistic activities on the surface of lymphoid cells: the induction of capping by its own receptors and the inhibition of the motility of a variety of receptors, including its own receptors.

The dimeric derivative, succinyl-Con A, is as effective a mitogen as the native lectin but lacks the ability to modulate cell surface receptor mobility. The data suggest that neither extensive immobilization of cell surface receptors nor capping is required for cell stimulation. Other studies on the modulation of receptor translocation suggest the hypothesis that there is a connecting network of colchicine-sensitive proteins that binds receptors of different types and mediates their rearrangement. The degree of connectivity of this postulated network appears to be altered by changes in the binding state of various surface receptors to the network. Thus, the network could provide the cell with a means to transmit signals, such as the stimulation for mitosis by lectins or antigens.

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