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Anatomy of the perfect catch: new light on the functioning of antibodies

A novel study paves the way for new therapeutic and biotech applications
   Like a goal-keeper executing a perfect catch. That's how antibodies react to the aggression of an foreign body. The image shows what a team of physicists of the University of Florence and Université d'Orléans have proved for the first time in an article published in Nature Scientific Reports (“Conformation-controlled binding kinetics of antibodies”, doi: 10.1038/srep18976).

Scientists Duccio Fanelli and Marta Galanti (Department of Physics and Astronomy - Inter-departmental Centre for the Study of Complex Dynamics and Francesco PIazza (Université d'Orléans, currently visiting Professor in Florence) have described with a mathematical model the dynamics with which antibodies bind themselves efficiently to antigens, foreign molecules, and mark them for elimination.

“From the point of view of the relation between its three-dimensional structure and its dynamics, an antibody expresses an unparalleled degree of perfection, explains Duccio Fanelli, associate professor of Condensed Matter Physics, that up until now we could only imagine from static images obtained from electronic microscopy or X-ray crystallography."

Antibodies have a three-lobe flexible structure, hinged on a common point and able to greatly modify their relative orientation. In the external part of the two upper lobes there are two identical active sites - regions whose amino-acidic sequence is extremely variable from one antibody to the next - that recognise and bind a large number of different antigens, irrespectively of their dimensions.

“We have elaborated a simplified model of the antibodies' flexible structure, comments Francesco Piazza, replacing the lobes with rigid structures made of spheres, bound so as to preserve their shape. Comparing the computer-generated simulations with experimental data available, we have discovered that the dynamics of the simplified antibody reproduces exactly the one measured. Thanks to its extreme flexibility, the antibody moves its "arms" in the same way a goal keeper would to intercept a ball.”.

The mathematical model permits to measure the capture rate of each antibody, that is the number of antigens captured per unit of time, showing the kind of relationship existing between the 3D structure of the antibodies, their dynamics and their biological function.

“To understand antibodies' dynamics, comments Fanelli, is the first step in opening new paths toward the utilisation of such proteins in a more effective way, creating purposefully engineered version for biotech and therapeutic applications.”

three-dimensional atomic structure of an antibody

29 January 2016